Abstract: In recent years, with the increased incidence of metabolic syndrome (MS), the number of MS patients with depression has increased accordingly. Insulin resistance, cortisol increase, immune inflammation activation, oxidative stress and autonomic nervous regulation disorder in MS are related to the occurrence of depression, and unhealthy living habits of depressive patients are the causes of MS. Exploring the relationship between the two diseases is helpful to study the pathogenesis of the diseases for the prevention and treatment of MS-related depression. The study mainly discusses the relationship between MS and depression based on epidemiological and clinical studies, and then summarizes the possible pathophysiological mechanism of comorbidity of MS and depression. Published studies suggest that the co-pathogenesis of MS and depression is caused by the interaction of multiple genetic and environmental factors but specific pathogenesis is still unclear and needs further study.