Depression is a common mental disorder that adversely affects human health and quality of life. Although its pathogenesis remains unclear, a large number of studies in recent years have indicated a close association between depression and mitochondrial dysfunction. This paper explores the mechanism of mitochondrial dysfunction in depression from four aspects: energy metabolism disorders, oxidative stress and inflammatory responses, mitochondrial DNA damage and mutations, and the imbalance of the mitochondrial quality control systems. Additionally, it summarizes 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 mitochondrial biogenesis, dynamic function, and autophagy. These insights offer new perspectives for the in-depth study of the pathogenesis of depression and its treatment with TCM.