Depression is the main cause of disability, and the adverse effects on people are difficult to eliminate. Despite the increasing number of antidepressants, depression is still not adequately treated clinically, and new mechanisms still need to be explored. As the beneficial effects of irisin on the nervous system are gradually elucidated, studies have found that irisin has an antidepressant effect, and irisin may become a new target for the treatment of depression. This study aims to explore the mechanism of irisin and its upstream and downstream antidepressants, by reviewing the existing studies to explain the link between depression and irisin, propose the potential mechanism of SIRT1 / PGC-1α mediating FNDC5/Irisin to regulate BDNF and promote neurogenesis to improve depression, and provide a new idea for the study of irisin and its upstream and downstream antidepressants.