Abstract: With the rapid development of biomedicine, a series of studies have shown that there is a close relationship between depression and intestinal microorganisms. Patients with depression are usually accompanied by changes in the species, relative abundance and metabolites of intestinal microflora. Short-chain fatty acids, the metabolites of intestinal flora, are important mediators that connect the host and intestinal flora. They have biological effects and affect the physiological function of the host. In recent years, the prevention and treatment of depression based on short-chain fatty acids has been a hot topic in this field. The content of short-chain fatty acids in the intestinal tract affects the occurrence and development of depression. This article mainly reviews the possible mechanisms of SCFA on depression (regulating hypothalamus-pituitary-adrenal axis, affecting tryptophan metabolism and reducing inflammation) and the possible ways of exogenous intervention in the treatment of depression (edible probiotics, probiotics and fecal flora transplantation), in order to provide theoretical reference for the development of new depression treatment drugs.