Abstract: Ginseng is a traditional Chinese medicine known as the "king of herbs" since ancient time in China. It was found in animal experiments that total saponins, ginsenoside monomers or glycosides from ginseng extraction all showed antidepressant effects in chronic unpredictable stress, corticosterone or lipopolysaccharide induced depression models. Taking ginsenosides as the focus, we reviewed the antidepressive mechanisms from the perspectives of various hypotheses, such as regulations of hypothalamic-pituitary-adrenal axis, monoamine neurotransmitter and neuroplasticity related to the pathogenesis of depression. The mechanism, target and pharmacodynamic targets of ginsenosides for anti-depression were summarized, in order to provide references for multi-targets and multi-level development of new anti-depression drugs, and improvement of diagnosis and treatment of depression from the perspective of traditional Chinese medicine and natural products.