Globally, diabetic nephropathy (DN) is the foremost cause of end-stage renal disease. With the incidence of diabetes increasing day by day, DN's occurrence is expected to surge to pandemic proportions. Current available therapeutic interventions associated with DN emphasize blood pressure, glycemia and lipid control while ignoring DN's progression mechanism at a molecular level. This review sheds light on the molecular insights involved in DN to help understand the initiation and progression pattern. Further, we summarize novel strategies with reported applications in developing a nanomedicine-based platform for DN-targeted drug delivery to improve drug efficacy and safety.