St. John's Wort (Hypericum perforatum) is an herb used to treat mild to moderate depression. It is available in pill form, as an infusion, in liquid extract form, and as a tincture. Its efficacy is a matter of some debate, but many studies conducted in the United States and Germany showed it to be effective in treating moderate depression, and it is routinely proscribed for this condition in Germany. However, St. John's Wort has been shown to be ineffective against severe depression and dysthymia.

Wort is an archaic word meaning "plant," and St. John's Wort gets its name from its traditional date of harvest, St. John's Day, or 24 June. It has small yellow flowers and perforate leaves characterized by small holes. St. John's Wort is grown commercially, but it is also a pest in many areas, as it can be poisonous to livestock if eaten in sufficient quantities. St. John's Wort can cause a number of problems in livestock, including restlessness, mania, skin irritation and lesions, depression, anorexia, miscarriage, and hypersensitivity to water and/or light. It can also push desirable vegetation out of an ecosystem by overtaking its niche.

St. John's Wort has a long history as a medicinal plant, though it was not always used for depression. Various species of Hypericum were used medicinally in Ancient Greece and in the Americas since before the arrival of Europeans. Native Americans used St. John's Wort topically as an astringent, antiseptic, and anti-inflammatory, and internally to induce abortions. Because of this property of St. John's Wort, the herb can have adverse effects on the fertility of the user and may interfere with birth control. St. John's Wort also has varied uses in homeopathic medicine.

In general, St. John's Wort has a much lower incidence of side effects than commercial anti-depressants. Its documented side effects include disorientation, dizziness, fatigue, gastrointestinal distress, sedation, and the aforementioned reproductive side effects. It can also cause photo sensitivity, or sensitivity to light, in both humans and animals, but this effect is rare.