Kidney injury resulting from drug-induced nephrotoxicity remains a significant global health concern, particularly in underdeveloped and developing countries where access to advanced medical care is limited. Among commonly implicated nephrotoxic agents, gentamicin (GEN), an aminoglycoside antibiotic widely used in the treatment of severe bacterial infections, has been strongly associated with renal toxicity. Despite its clinical effectiveness, rapid bactericidal action, and relative affordability, the therapeutic use of gentamicin presents a notable paradox due to its potential to cause significant kidney damage when administered at therapeutic or prolonged doses. This challenge underscores the importance of understanding the mechanisms of gentamicin-induced nephrotoxicity and identifying reliable biomarkers for early detection and monitoring of renal dysfunction. Gentamicin-induced nephrotoxicity is primarily characterized by oxidative stress, renal tubular necrosis, and impaired glomerular filtration. The underlying mechanism involves the excessive production of reactive oxygen species (ROS), which overwhelms the endogenous antioxidant defense system of the kidney. The accumulation of ROS leads to oxidative damage of renal tubular epithelial cells, resulting in structural and functional impairment of the kidneys. Consequently, this damage reduces the glomerular filtration rate (GFR) and leads to elevated levels of biochemical markers such as serum creatinine and urea, which are commonly used indicators of renal dysfunction. In addition to these traditional markers, the urine protein-creatinine ratio (UPC) has emerged as a clinically valuable index for assessing renal injury and monitoring proteinuria. The UPC provides a convenient and reliable measure of protein excretion relative to creatinine levels in urine, thereby offering insight into glomerular integrity and kidney function. Because creatinine excretion remains relatively stable in individuals with normal renal function, changes in the UPC ratio serve as a sensitive indicator of glomerular damage and disease progression. As a result, the UPC has gained widespread acceptance in clinical and experimental studies as a useful tool for evaluating kidney injury. Understanding the pathophysiological mechanisms underlying gentamicin-induced nephrotoxicity and the role of reliable diagnostic markers such as the urine protein-creatinine ratio is essential for improving early detection and management of renal injury. Such knowledge is particularly important in resource-limited settings where gentamicin continues to be widely used due to its affordability and effectiveness. Consequently, further research into strategies that can reduce oxidative stress and preserve renal function is crucial for minimizing the adverse effects associated with gentamicin therapy and improving patient outcomes.