Abstract
Major Depressive Disorder (MDD) is a severe, chronic illness for which conventional treatments often show limited efficacy and side effects, driving a renewed interest in traditional medicinal plants. The therapeutic promise of these plants lies in their multi-targeted action, influencing neurotransmitter systems, modulating neuroinflammation and oxidative stress, impacting neuroplasticity, and regulating the Hypothalamic-Pituitary-Adrenal (HPA) axis. Despite their clinical potential, the use of medicinal plants is associated with challenges, including complex pharmacokinetics, significant adverse effects, and the risk of herb-drug interactions, alongside concerns regarding standardization and quality control. This manuscript aims to examine the therapeutic potential of key medicinal plants for managing MDD, including Hypericum perforatum, Rhodiola rosea, Melissa officinalis, Passiflora incarnata, Valeriana officinalis, and Cannabis sativa. Additionally, the review addresses emerging candidates such as Curcuma longa, Withania somnifera, Panax ginseng and Centella asiatica. By focusing on their mechanisms of action, pharmacokinetics, and associated risks, this review provides a more comprehensive understanding of their role in modern psychiatric care.