Background: development of aminoglycosides antibiotics assisted in the cure of infective diseases, Gentamicin (GM) is a well known example that has a wide antibacterial domain.This clinical effect is restricted by the occurrence of kidney functions impairment . Aim of the work: we performed this study to examine possible protective effects of Ramipril, Alpha lipoic acid (ALA) and their combinations on kidney functions impairment caused by GM in rats. Materials and Methods: fifty male albino rats were categorized into five groups of ten rats. The first group served as control, the second group received GM, the third group received Ramipril and GM, the fourth group received ALA and GM, the fifth group received Ramipril, ALA and GM. Serum biochemical parameters and kidney homogenate oxidative stress parameters were utilized for evaluation of the nephrotoxicity. Results: pretreating rats with Ramipril or ALA or their combination attenuated GM induced nephrotoxicity. Conclusions: administration of Ramipril alone, ALA alone, or their combination possessed various degrees of nephroprotection against Gentamicin induced nephrotoxicity in rats.