Objective: This study aimed at exploring the therapeutic efficacy of L-Carnitine (LC) against cisplatin-induced nephrotoxicity (CIN) by assessing oxidative stress response, and relevant gene expression in rat kidney tissues. Methods: Rat CIN model was induced by intraperitoneal injection of Cisplatin (Cis). Eighteen male Sprague-Dawley mature rats with age (6 weeks) weighing 180 ± 20 gm were randomized to receive either control (saline), Cis or Cis + LC. Markers of oxidative stress (superoxide dismutase (SOD) and Malonaldehyde (MDA) and Bax and BCL-2 gene expression profiles were assessed thereafter.   Results: Cisplatin administration showed a marked increase in oxidative stress as evidenced by elevated MDA and diminished SOD levels, and changes in gene expressions of apoptosis-regulating genes (BCL2, BAX). Remarkably, treatment with LC normalized most parameters and achieving gene expression levels comparable to control groups. Conclusion: Our findings highlight the significant nephroprotective potential of LC against CIN, pivoting the way for bigger clinical studies and incorporation into clinical care guidelines.