Abstract We designed this work to examine the curative role of l-carnitine (LCAR) in a rat model of cisplatin (CDDP)-induced kidney injury. We induced kidney injury in rats by a single intraperitoneal injection of 5 mg/kg of CDDP. Fifteen days post injection, rats were orally supplemented with 354 mg/kg of LCAR for another 15 days. Kidney tissues were subjected to histo-biochemical analysis along with mRNA gene expression quantification for cytoskeleton proteins encoding genes (vimentin, nestin, and connexin 43) by real-time reverse transcription polymerase chain reaction. LCAR reversed CDDP-induced renal structural and functional impairments. LCAR significantly declined serum urea and creatinine concentrations, restored oxidant/antioxidant balance, reversed inflammation, and antagonized caspase 3-mediated apoptotic cell death in renal tissues. Moreover, LCAR effectively down-regulated cytoskeleton proteins mRNA levels; reflecting amelioration of CDDP-provoked podocyte injury. We concluded that LCAR has a favorable therapeutic utility against CDDP-induced kidney injury.