14 Natural Antidepressants That Health Experts Say Work

Updated on May 22, 2025

Natural antidepressants aren’t a cure-all, but science has found certain supplements may relieve symptoms—no prescription necessary.

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Experts

  • Erik Modlo, MD, MBA, IFMCP, is a Functional Medicine Physician at Cleveland Clinic and has over 15 years of experience in internal medicine. He serves as the Educational Director at the Center for Functional Medicine at Cleveland Clinic.
  • Gary Soffer, MD, FAAP, is the director of the integrative medicine program at Yale Medicine and Smilow Cancer Hospital. He is also an Associate Professor of Pediatrics and the Director of the Pediatric Residency Program at Yale School of Medicine.
  • Michelle DiBlasi, DO, is a psychiatrist, Chief of Inpatient Psychiatry at Tufts Medical Center, and Assistant Professor at Tufts University School of Medicine.
  • Connie Zajicek, MD, is a board-certified Child, Adolescent, and Adult Psychiatrist at Memorial Hermann Health System in Houston, Texas.
  • Beata Lewis, MD, is a Board-Certified Psychiatrist, Integrative Medicine Doctor, and a Clinical Assistant Professor of Complementary and Alternative Mental Health at NYU. She is also the chair of the New York County Psychiatric Society Integrative Psychiatry Committee and the Co-Chair of the National APA Integrative Psychiatry Caucus.
  • Jess Henning, APRN-CNP, IFMCP, is a nurse practitioner with the Center for Integrative Health at The Ohio State University Wexner Medical Center. She also works as a family medicine nurse practitioner with Primary Care New Albany and is an Ambulatory Advanced Practice Provider.

Highlights

  • Natural antidepressants are substances like herbs, plants, and dietary supplements that have been researched for potential antidepressant properties.
  • They can be an effective tool in a depression treatment plan, according to experts.
  • Natural antidepressants do not replace conventional treatments, however.
  • Any supplement or herb can pose risks—so it’s important to work with your doctor when using natural antidepressants.  

Natural antidepressants are substances obtained from natural sources—including plants, herbs, or dietary components—that may possess antidepressant properties, explains Erik Modlo, MD, MBA, IFMCP, a Functional Medicine Physician at Cleveland Clinic. And with depression rates on the rise—an estimated one in five U.S. adults struggle with mental illness, per the National Institutes of Mental Health—researchers and experts are exploring the potential of natural antidepressants as a complementary tool for mental health treatment. 

We’re still learning about the underlying mechanisms of depression, but neurotransmitters like serotonin and dopamine clearly play a role,” explains Gary Soffer, MD, FAAP, director of the integrative medicine program at Yale Medicine and Smilow Cancer Hospital. “Many natural supplements aim to regulate these, while others may help reduce inflammation—another factor thought to contribute to depressive symptoms.”

That said, it’s very important to first talk to your doctor about starting a supplement or natural antidepressant, especially if you have known medical conditions or are taking other medications, says Michelle DiBlasi, DO, Chief of Inpatient Psychiatry at Tufts Medical Center. “Supplements may lower or increase the effectiveness of other medications you are taking, which can be particularly dangerous,” she explains. “People should also be aware that natural remedies may also vary in terms of dosing depending on the brand, so it is especially important to discuss with your doctor ahead of time before starting them.”

How do natural antidepressants work?

Natural antidepressant supplements can work in different ways and through different mechanisms. “Most commonly, they provide the brain with the building blocks needed to make neurotransmitters,” explains Connie Zajicek, MD, a Board-Certified Child, Adolescent, and Adult Psychiatrist at Memorial Hermann Health System

Neurotransmitters include serotonin and dopamine, which each play a major role in regulating our mood, she says. “Supplements can, therefore, affect the amount of or efficiency with which our brain produces and uses neurotransmitters leading to improved mood regulation.” 

“I always recommend optimizing the diet first,” Dr. Soffer adds. “After all, supplements should be just that—a supplement to good nutrition.” But there are cases where it’s tough for someone to get enough of a certain nutrient from diet alone. 

In addition, dietary intake typically takes longer to correct an imbalance, and supplements can be used to jump-start the process while a person is learning how to change their diet, explains Jess Henning, APRN-CNP, IFMCP, a nurse practitioner with the Center for Integrative Health at The Ohio State University Wexner Medical Center. 

14 Natural antidepressants to try today

“Supplements are very helpful, and they’re just part of the toolbox for addressing depression,” says Beata Lewis, MD, a Board-Certified Psychiatrist, Integrative Medicine Doctor, and a Clinical Assistant Professor of Complementary and Alternative Mental Health at NYU.

But each person is different—and treatment should be tailored, monitored, and adjusted with the support of a medical professional. “I rarely recommend just one supplement,” she explains. “I typically combine several based on each patient’s specific lab results.” 

Dr. Modlo also points out that while some natural products, or “nutraceuticals,” show promise, more high-quality research is needed. Concerns regarding standardization and long-term safety exist as well, as supplements are not regulated by the U.S. Food & Drug Administration (FDA). 

That’s why Dr. Lewis recommends rechecking labs at least once a year to adjust a supplement protocol as things change. In addition: “Quality matters,” she says. “It’s best to use pharmaceutical grade supplements that are well researched, formulated, and tested.” 

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1. St. John’s Wort

St. John’s Wort is a plant that research shows can work as well as some common depression medicines (for mild to moderate depression), but generally with fewer side effects, Dr. Modlo says. The typical dose used in research is 300 milligrams (mg) three times a day. “It usually starts working in 4 to 6 weeks.”

However, it’s important to know that St. John’s Wort has many drug interactions, meaning it can affect how other medicines work. “It might make some medicines, like blood thinners or birth control, less effective or cause more side effects,” Dr. Modlo says. There are also concerns over the safety of its long-term use. 

It should also not be combined with other antidepressants. “St. John’s Wort works by increasing certain neurotransmitters, including serotonin, so it can interact with other serotonergic medications or supplements, potentially causing a rare but serious complication called serotonin syndrome,” Dr. Zajicek says. 

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2. Omega-3

“Using omega-3 fatty acid supplements is usually seen as a good option for people who are struggling with depression,” Dr. Modlo says. “Some studies say that taking 1 to 2 grams of EPA (eicosatetraenoic acid) each day can be helpful.” When looking for an omega-3 supplement, he says that products with a greater ratio of EPA compared to DHA (docosahexaenoic acid, another type of fatty acid) seem to work best. 

This is because EPA is thought to reduce inflammation and improve neurotransmitter function, specifically serotonin, Dr. Zajicek says. “For some patients, it makes a huge difference in inflammation markers,” Dr. Lewis adds. 

While eating foods like fatty fish can give you omega-3s and is good for your health, it can be hard to get enough only from food, Dr. Modlo says. “So, taking supplements can be a good and easy way for people with depression to get what they need.” 

However, Dr. Zajicek cautions that omega-3 fatty acids can increase the risk of bleeding, cause gastrointestinal upset, and interact with certain medications, including warfarin, aspirin, and certain nonsteroidal anti-inflammatory drugs (NSAIDs). 

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3. L-methylfolate

L-methylfolate is a supplemental form of folate—vitamin B9—that can potentially reduce the severity of depression if someone is deficient, Dr. Zajicek says. 

This is because folate gets converted to methylfolate in the body, which is then used to make neurotransmitters, including serotonin, she explains. 

You can get folate in your diet from foods like:

  • Leafy greens
  • Cruciferous veggies
  • Legumes
  • Seeds

Still, Dr. Zajicek notes, “There are also people who are deficient in an enzyme required to produce methylfolate (from folate)—therefore, taking a supplement of methylfolate can improve the body’s ability to make appropriate levels of serotonin.” A blood test is required to test for these deficiencies and determine appropriate dosing. 

“Several meta-analyses show that folate works well alongside standard antidepressants,” Dr. Lewis says. “It’s important to make sure that patients take folate and not folic acid.” 

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4. Other B vitamins

“For some individuals, B vitamins can help with depression symptoms,” Henning says

“B vitamins are associated with a few important processes in our body—the detoxification of toxins, hormones, and waste from the body, the process of turning on and off genes that may lead to chronic disease, and the production of neurotransmitters like serotonin and dopamine which are involved in depression.”

“We know that vitamin B deficiencies—including B6 and B12—can worsen mood,” Dr. DiBlasi says. “For someone with a deficiency in a B vitamin, a supplement is a good idea.” However, it is also important to continue to try to eat a well-balanced diet in addition to taking a supplement. 

I recommend lab testing with your healthcare provider to determine if you are low in B vitamins and strategically supplementing where needed,” Henning says. She also encourages a diet rich in B vitamins, including foods like:

  • Dark leafy greens
  • Eggs
  • Beans
  • Beets
  • Sunflower seeds
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5. Vitamin D

Low vitamin D levels have been linked to depression, says Dr. Soffer. “It is important to get your levels measured, but if they are low, supplementation may help, and the risk is low.” 

The link between vitamin D deficiency and depression is due to vitamin D’s involvement in producing serotonin—one of the “happiness” neurotransmitters, Henning explains. 

Vitamin D deficiency is more common than you might think—according to the Cleveland Clinic, approximately 35% of Americans have vitamin D deficiency. Many more people likely have lower-than-ideal levels, or “insufficiency,” according to 2025 research from the National Institutes of Health (NIH). 

“It is especially more prevalent in places that don’t get a lot of sunlight year-round, like the Northeast, since vitamin D is mostly made in your body after exposure to sunlight and is often not found naturally in many foods,” Dr. DiBlasi says. “Low vitamin D can certainly worsen depression, so this is something to discuss with your doctor.”

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6. 5-HTP (5-hydroxytryptophan)

HTP (5-hydroxytryptophan) is made by the body from tryptophan (an amino acid) and is used to make serotonin, Dr. Zajicek explains. You can’t get it from food—but you can eat foods rich in tryptophan to support 5-HTP production. These include:

  • Animal products, like chicken, dairy, and fish
  • Soy products, such as tofu
  • Legumes 
  • Nuts and seeds

“It can also be taken as a supplement and may work by increasing serotonin levels, which is a neurotransmitter involved in mood regulation.” However, she says that the studies are small and have a short treatment duration. 

“It can cause serious side effects if taken in larger doses or if combined with other serotonergic medications (medications that increase serotonin),” Dr. Zajicek says. “It is also unclear what dose is effective.” The effects and safety of long-term use aren’t fully known, either.

So, it’s important to work with your doctor if you’re considering trying out 5-HTP. 

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7. Magnesium

“I also recommend antioxidants,” Dr. Lewis says. “A 2023 meta-analysis documented significant benefits from supplements like magnesium, zinc, selenium, and CoQ10 (Coenzyme Q10, commonly found as ubiquinone in supplements).” 

In particular, Dr. Modlo and Henning point to magnesium as showing positive effects on mood regulation and depressive symptoms. Research published in Nutrients in 2025 says that approximately 60% of adults don’t get enough magnesium in their diet, which comes from sources such as:

  • Leafy greens
  • Nuts and seeds
  • Whole grains
  • Legumes 
  • Fish

Studies have shown an improvement in depressive symptoms when an individual with low magnesium supplements magnesium,” Henning says. “This is why seeing a healthcare provider and testing levels can be helpful.” 

As a bonus, magnesium can help you sleep better, too—and better sleep is associated with depression recovery. Read more about how taking magnesium for a month helped our senior editor get the best sleep of her life.

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8. Zinc

Dr. Modlo and Henning say that research suggests zinc could be a natural antidepressant as well—if you’re deficient in the mineral. 

There is some evidence that lower zinc levels are associated with depression or depressive symptoms,” Henning says. Zinc deficiency is less common, but older adults are at risk for sub-optimal levels, according to the NIH.

“If needed, a supplement is fine, or you can incorporate foods high in zinc into your diet, like pumpkin seeds, hemp seeds, and avocado,” says Henning. 

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9. Saffron 

“Clinical trials have demonstrated that saffron can significantly reduce depressive symptoms,” Dr. Soffer says. Research published in the Yale Journal of Biology and Medicine in 2024 says its effects are comparable to standard antidepressant treatments for mild to moderate depression. 

Still, more studies are needed. While the research says that saffron’s use as a natural antidepressant is supported by scientific evidence, there aren’t yet guidelines for its use, dosing, and long-term outcomes. 

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10. Curcumin

In addition to saffron, Dr. Modlo says that curcumin—the active ingredient in turmeric—has been studied for its anti-inflammatory and antioxidant properties, showing some support for use in depression treatment. 

However, like saffron, while curcumin shows anti-depression, anti-anxiety, and anti-stress properties, further research is needed to determine optimal dosing, treatment duration, and possible side effects, per 2024 research published in Life. The research does state that based on current scientific knowledge, a formulation known as Theracurmin seems to be the most effective form of the supplement. 

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11. Lavender

Lavender has been shown to ease anxiety and depression, likely through effects on neurotransmitters and calming the nervous system, Dr. Soffer says. More high-quality research is needed, according to the National Center for Complementary and Integrative Health (NNCCIH), but small studies have shown that oral lavender capsules or lavender tea might reduce depressive symptoms. 

Topical lavender does not seem to have any effect, but aromatherapy with lavender oil may help some people. In general, the NCCIH says lavender products are considered safe, but some side effects like headache or nausea have been reported. 

“However, [lavender] may have activity on estrogen receptors and should be used with caution in those with hormone-sensitive cancers and other related illnesses,” Dr. Soffer says. 

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12. SAMe

S-adenosylmethionine, or SAMe, is effective in reducing depressive symptoms, especially alongside conventional antidepressants, says Dr. Modlo. It’s generally well-tolerated with only minor side effects reported, including nausea, Dr. Zajicek says. But it can interact with other antidepressant medications and supplements. 

Still, Dr. Lewis says that while the evidence base for SAMe in easing depressive symptoms is strong (it works similarly to folate/L-methylfolate), there are concerns about using it long-term. 

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13. Glutathione

“I used to use SAMe in my practice, but recently, I’ve shifted toward using glutathione in forms that can cross the blood-brain barrier,” Dr. Lewis says. “I’ve found this approach particularly effective for addressing the oxidative stress component that often accompanies depression.”

Glutathione is an antioxidant that’s naturally produced in our bodies, but its levels can drop due to factors like stress, poor nutrition, and age. 

Research published in Clinics and Practice in 2023 found that reduced levels of glutathione in the brain increase the risk of developing psychiatric issues, such as depression. While the research is promising, it’s still in its early stages, so make sure to check with your doctor before using glutathione. 

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14. Probiotics

“Emerging evidence suggests gut microbiota may affect mood, with probiotics potentially improving depressive symptoms,” Dr. Modlo says. And what’s especially exciting about the latest research—like this 2025 study published in the Journal of Affective Disorders—is that probiotic supplementation shows promising effects in treating major depressive disorder, not only mild to moderate symptoms. 

Read more about how one woman healed her gut with probiotics, relieving her depression

What to know about using supplements for depression

“Supplements may offer gentle support, but they’re not a cure-all,” Dr. Soffer emphasizes. “They should not replace therapy, lifestyle changes, or medication when needed.” 

What’s more, he says that “natural” doesn’t mean harmless, and many supplements can interact dangerously with medications or cause side effects. “Healing is most sustainable when it’s safe, informed, and collaborative—so it is vital you are open and transparent with your healthcare providers.” 

In fact, the American Psychiatric Association emphasizes that postponing established treatments in favor of complementary and alternative medicine therapies can lead to considerable risks, including the potential exacerbation of depressive symptoms and delays in receiving effective care, Dr. Modlo explains. 

Why personalized care works best

Safety is critical when using natural antidepressants, but you also save yourself time and frustration by working with a medical provider who can help personalize your natural antidepressant care. 

One common misconception is that taking more of something our body needs must be good,” Dr. Zajicek says. Unfortunately, this is often not the case. “Our bodies typically can only utilize a set amount of a substance, and adding more will only lead to our body excreting the excess or causing side effects.” For example, if you start to take vitamin D to relieve depression symptoms—but you’re not actually low in vitamin D—it’s unlikely to have any effect. 

“With this said, it is true that if a person is deficient in a certain neurotransmitter, enzyme, or vitamin, taking it in a supplement can be beneficial,” Dr. Zajicek explains.

The same wisdom goes for other ways to naturally relieve depression, such as dietary changes and body therapies, Henning says. “For example, a ketogenic diet or intermittent fasting is not ideal for every body type.” 

She recommends establishing a relationship with a healthcare provider who knows your health history and preferences and can help you build an appropriate, safe plan to address your needs and get the best outcomes. “There is a lot of information available these days, and having a provider to ‘run it by’ can save time, reduce anxiety over choosing from all the things available, and improve your results.” 

Other ways to naturally relieve depression

“We use a multi-prong approach to treat depression because it is not always a one-size-fits-all solution,” Henning says. Each individual is unique, and being able to develop and implement an individualized plan based on that person’s diagnosis, lifestyle, and preferences can help increase success. 

She adds, “There are many ‘levers’ we can pull on to treat depression, so why not use everything we can? This may include diet changes, exercise or movement, bodywork like osteopathic manipulation, acupuncture or massage, supplements, and/or medication.” 

Eat mood-boosting foods

Diet and intake of nutrients can impact the risk for depression and depressive symptoms in individuals,” Henning says. “Vegetables and fruits in the diet are associated with a lower risk for depression or depressive symptoms.”

She typically recommends a Mediterranean diet. “This diet does not contain processed foods or added sugar, which have been associated with increased risk for depression and increased expression of depressive symptoms.” 

At the end of the day, it’s hard to tell if a single nutrient, mineral, or vitamin is the key to supporting an individual’s depression recovery, she says. “The best defense or support of depression is to eat a diverse, colorful diet rich in whole foods like vegetables, fruits, and omega 3 fatty acids (chia seeds, flax seeds, hemp seeds or seafood like salmon and sardines).” 

And while too much coffee may make you anxious and jittery, the American Medical Association says that in low doses—20 to 100 milligrams at a time—caffeine may help relieve depressive symptoms, too. 

Want more inspiration? Nutrition and brain experts say that these are the seven best mood-boosting foods

Connect with others

We know that connection can be a really critical piece for recovery from depression,” Dr. DiBlasi says. “When someone is depressed, it is important for them to know that those that are close to them still care about them and are there for them, even if they are not able to fix the depression.” 

It can feel impossible to socialize when you’re in the thick of depression. However, a 2023 review of research published in the Health Education Journal found that even just texting a friend twice a week has the potential to reduce depressive symptoms.

Other research, published in Frontiers in Health Services in 2024, says that human-animal interaction, like playing with your pet, may help lessen symptoms of depression as well. 

“There are also many different types of psychotherapy, including cognitive-behavioral therapy (CBT), dialectical behavioral therapy (DBT), interpersonal therapy (IPT), and mindfulness-based cognitive therapy that have been shown to be helpful for depression,” Dr. Zajicek says. 

Mental health is complex, and support should be too—so don’t go it alone,” Dr. Soffer emphasizes.

Pay attention to your body

“Self-care practices are a critical part of depression symptoms,” Dr. DiBlasi says. “When you are depressed, it can feel really daunting to have the energy to exercise, go out with friends, or do other things you enjoy, but even small acts of self-care can be very helpful.” 

She recommends that people start small, even if it’s just doing little things to get going, like:

  • A few minutes of exercise or light stretching
  • Smiling
  • A short meditation
  • Spending a few minutes outside
  • Phoning a friend who lifts you up

Maybe you work your way up to going out to get a massage, head out for longer walks outside, or indulge in some luxurious “me time.”Like most things, lifestyle modifications take practice to become habit and remain consistent,” Dr. Zajicek says. 

Meditation

According to the American Psychological Association, more than 200 studies agree that mindfulness-based therapy, including meditation, can help:

  • Reduce depression, anxiety, and stress
  • Strengthen your brain against stress and negative thoughts and emotions
  • Significantly reduce relapse in people who have had major depression in the past
  • Improve overall physical health

From a physical standpoint, meditation produces a physiologic response—reducing heart rate, blood pressure, and breathing rate, which lowers feelings of anxiety, Dr. Zajicek says. “Meditation also promotes mindfulness, a concept that includes refocusing our perspective to the present, diminishing the negative preoccupation with future fears or previous mistakes that people often dwell on.” 

Don’t know where to start? There are many apps that help guide and track your meditation—or check out Deepak Chopra’s go-to meditation for happiness

Change your routine

“Changes to your routine can absolutely help support depression recovery,” Henning says. 

She recommends:

  • Ensuring adequate sleep—at least seven to nine hours a night
  • Regular exercise
  • Prioritizing a healthy diet (her go-to is the Mediterranean Diet)
  • Spend at least two hours a week outdoors

Following these standard recommendations opens up opportunities to take baby steps toward larger, meaningful changes to your routine, like finding passion in a new hobby. 

For instance, as you aim for better sleep, you may develop a calming nighttime routine complete with stretching by candlelight, soothing skin care, and swapping your phone screen for a book. Or, prioritizing nutrition could inspire your inner chef, while spending more time outside may ignite a love of gardening. 

Changing your routine means taking breaks from your day-to-day life, too. Even if you can’t take a vacation, simply spending the day visiting a new place nearby can help you mentally reset. Henning suggests: “Your local county or state park system is a great place to start to explore and get outside!” 

Go easy on yourself

“I think a lot of times people struggle with negative thoughts, especially when they are depressed,” Dr. DiBlasi says. 

She says that when she’s getting down on herself, rather than saying, “I can’t do this” she changes that phrase in her mind to: “I am presently struggling with this.”

“I then remind myself that even if I am struggling currently, I have the power to start focusing on things I can improve and start to look to improve the situation,” she shares.

Dr. Modlo suggests some other phrases you can use as positive affirmations (which experts and science say have clear benefits): 

  • “I am competent, and I am worthy of positive things.” This statement aids in transforming self-doubt into confidence and self-esteem.
  • “I decide to concentrate on what I can influence and release what I cannot.” This is ideal for managing feelings of being overwhelmed or frustrated.
  • “I am evolving each day, and obstacles are chances for growth.” A gentle reminder that progress, rather than perfection, is what truly counts.

When to see a doctor for depression

If you are having any thoughts of harming yourself or others, it is important to be seen by a healthcare provider immediately, Henning says. You can also connect with the National Mental Health Hotline 24/7 by calling or texting 988, or visit their website to live chat with a specialist and access deaf or hard-of-hearing resources. All conversations are free and confidential. 

Still, sometimes depression doesn’t feel urgent—but it’s still impacting your daily life. This could look like:

  • Not getting out of bed
  • Not seeing friends as often as you used to
  • Loss of interest in hobbies 
  • Sleeping more or less than normal (and/or feeling exhausted even after resting)
  • Unusual changes to your appetite and/or weight
  • Inability to focus, make decisions, or remember things

If you have symptoms like these that last for more than two weeks, that’s a clue to talk to your doctor, Henning says. 

She also advises checking in on your mental health with your primary care provider regularly, like during an annual physical. “They will often have you do a Patient Health Questionnaire (PHQ)-9 and a Generalized Anxiety Disorder (GAD)-7,” she says. “These are questionnaires to assess depression and anxiety in individuals and help guide treatment. Your primary care provider can then provide care or help facilitate a referral if needed.” 

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