Background and Objectives: Depression is a serious, debilitating and common illness among various social groups. Chemical and synthetic drugs available for the disease have numerous side effects and only 50% result in full recovery. Today, researchers attention has been shifted toward natural compounds. Medicinal plants showed considerable pharmacological effects in the treatment of depression in different experimental models. Material and methods: In this study, articles from journals indexed in the Scopus, PubMed, Information Sciences Institute (ISI), and Scientific Information Database (SID) were reviewed. Findings: A review of studies in this field showed that most medicinal plants show anti-depressant effects through regulating of synaptic serotonin and dopamine, regulating the activity of the hypothalamus-pituitary-adrenal axis, strengthen the antioxidant defense system and reducing inflammatory mediators. Conclusion: medicinal plant and their component show protective effect against depression through different mechanism. Medicinal plants can provide new source for the development of drugs against depression.