Diabetic kidney disease (DKD) has a high incidence and mortality rate and lacks effective preventive and therapeutic methods. Apoptosis is one of the main reasons for the occurrence and development of DKD. Mesenchymal stem cells (MSCs) have shown great promise in tissue regeneration for DKD treatment and have protective effects against DKD, including decreased blood glucose and urinary protein levels and improved renal function. MSCs can directly differentiate into kidney cells or act paracrine mechanisms to reduce apoptosis in DKD by modulating signaling pathways. MSC-derived extracellular vesicles (MSC-EVs) mitigate apoptosis and DKD-related symptoms by transferring miRNAs to target cells or organs. However, studies on the regulatory mechanisms of MSCs and MSC-EVs in apoptosis in DKD are insufficient. This review comprehensively examines the mechanisms of apoptosis in DKD and research progress regarding the roles of MSCs and MSC-EVs in the disease process.