The kidney is more susceptible to poisoning than any other organ in the body because of the number of poisons that are delivered to it. By 2040, it is anticipated that kidney diseases will rank fifth in terms of causes of mortality. Drug-induced nephrotoxicity has been identified as a significant contributor to kidney damage. Gentamicin (GM), the most widely prescribed aminoglycoside (AG) antibiotic, is still utilized in clinical practice despite the fact that it can induce nephrotoxicity due to its strong bactericidal properties, broad antibacterial spectrum, and low bacterial resistance. It has been demonstrated that GM raises the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the renal cortex, which ultimately results in renal injury. This study aims to discuss the pathogenesis of GM-related nephrotoxicity for clinical trials to uncover promising agents with reno-protective properties that can be used concurrently to counteract the nephrotoxicity of GM.