Abstract: Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes. With the increasing prevalence of diabetes, it has become an important cause of end-stage renal disease, which seriously threatens the life and health of patients and aggravates the medical burden of society. The dysfunction of mitochondria and endoplasmic reticulum (ER) plays a key role in the progression of DKD, and the mitochondria-associated endoplasmic reticulum membrane (MAM) is the core hub of the dynamic interaction between the two. Mitochondrial dynamics and apoptosis affect the pathological process of DKD. This article systematically reviews the multiple molecular mechanisms of MAM in the occurrence and development of DKD, reveals its involvement in the fine regulatory network of kidney injury by regulating calcium ion (Ca²⁺) balance, glucose metabolism, inflammatory response and autophagy, and clarifies how MAM dysfunction drives the transformation of DKD into end-stage renal disease. In addition, this article deeply explores the potential of MAM-related biomarkers in early diagnosis, as well as innovative therapeutic strategies such as drug intervention and gene repair targeting MAM, which provides theoretical references for basic mechanism research and clinical practice of DKD.