Polypharmacy, defined as the simultaneous use of multiple medications, is a widespread and complex clinical problem in modern medicine, particularly among elderly patients. Age-related physiological changes, especially the decline in renal function, significantly increase the nephrotoxic effects of medications in the setting of polypharmacy. This article analyzes the mechanisms through which polypharmacy affects renal function in the elderly, as well as the associated clinical risks and strategies for early detection and monitoring. The study findings demonstrate that optimization of drug therapy, regular laboratory monitoring, and an individualized clinical approach play a crucial role in preventing renal injury in elderly patients.