Depression is a common mental disorder with adverse effects on human health and quality of life. Although its pathogenesis remains unclear, numerous recent studies have indicated a close association between depression and mitochondrial dysfunction. This review explores the critical role of mitochondrial dysfunction in the pathogenesis of depression from the aspects of energy metabolism disorders, oxidative stress and inflammatory responses, mitochondrial DNA damage and mutations, and the imbalance of the mitochondrial quality control systems.We also summarize recent advances in the use of traditional Chinese medicine (TCM) to treat depression by regulating mitochondrial function. The findings show the potential of TCM in enhancing mitochondrial energy metabolism, reducing oxidative stress and inflammatory responses, improving mitochondrial DNA, and modulating the mitochondrial quality control systems, including for the in-depth study of the pathogenesis of depression and its treatment with TCM.