Comorbid diabetes and depression are a significant public health burden as the consequences of both diseases are worsened by each other. In this study, we have compiled and analyzed findings from various studies to demonstrate that diabetes has a strong association with depression. Both have a significant impact on the quality of life, although the exact mechanisms through which these two chronic diseases affect each other remain unknown. This article discussed the shared etiological factors of comorbidity between diabetes and depression, including physiological (e.g., deregulation of the hypothalamic-pituitaryadrenal (HPA) axis, sympathetic nervous system (SNS) overactivity, microvascular dysfunction, arterial stiffening, inflammation, and cytokines), behavioral (e.g., diet and lifestyle modifications), and environmental (e.g., childhood adversity, poverty, and neighborhood environment). Included data from a range of settings have suggested that the prognosis of both diabetes and depression, in terms of complications, treatment efficacy, morbidity, and mortality, is worse for either disease when they occur concurrently than individually. The implication for the physical, mental, and social well-being of depression in diabetes causes poor self-care and adherence to medical treatment. This article also highlights the importance of regular screening and prompts the treatment of comorbid diabetes and depression with pharmacotherapy, face-to-face psychotherapy, and non-face-to-face models of alternative psychological interventions, including information and communication technologies (ICTs), computer-based diabetes selfmanagement interventions, and digital mental health intervention, to improve the outcomes of both diseases.Categories: Endocrinology/Diabetes/Metabolism, Internal Medicine, Psychiatry Keywords: diabetes-related distress, impact of diabetes and depression on life, diabetes and depression prevalence, depression screening, comorbid diabetes and depression management, type 2 diabetes and depression, type 1 diabetes and depression, depression , diabetes and depression