Abstract: Depression, as a common mental disorder, is often alleviated and treated with antipsychotic drugs in clinical practice. However, long-term use of such drugs can lead to serious sequelae such as drowsiness, nausea and memory loss in patients. Therefore, effective prevention or relief of depression, reducing the pain and side effects of treatment for depressed patients and increasing the cure rate of depression have become current research hotspots. Polysaccharides are biologically active substances derived from natural products, and many studies have shown that polysaccharides in natural products are effective in alleviating depression. This paper reviews the effects and mechanisms of polysaccharides in natural products on the alleviation of depression by modulating neuronal dysfunction in the brain, modulating HPA axis abnormalities, modulating inflammation in the body, modulating microbial-gut-brain axis functions, and propose the cross-linking of polysaccharide products with drugs as a new therapeutic strategy for the prevention, alleviation and treatment of depression in the future based on these mechanisms of action. The study also suggests new targets and candidate compounds for the treatment of depression.