Abstract: Background and Objective: Oxaliplatin® is an antineoplastic platinum-based compound; nephrotoxicity is one of its most serious side effects. This study aimed to explore the nephroprotective potential of Costus Ethanolic Extract (CEE) against Oxaliplatin®-induced nephrotoxicity. Materials and Methods: Adult male Wistar rats, weighting 140-160 g, were randomly divided into four groups: (1) Normal rats, (2) Rats ingested with CEE (67.08 mg kg–1 day–1), (3) Rats injected (ip) with Oxaliplatin® (10 mg kg–1 week–1) and (4) rats treated with CEE in combination Oxaliplatin® injection. Results: After six weeks of treatments, the results revealed that CEE ingestion along with Oxaliplatin® injection markedly minimized the Oxaliplatin®-induced renal deterioration; this was evidenced by the significant reduction in serum urea, creatinine, uric acid, Tumor Necrosis Factor Alpha (TNF-α), Interleukin 1Beta (IL–1β) and Sodium ion (Na+) levels as well as kidney Malondialdehyde (MDA), Nitric Oxide (NO) and DNA fragmentation values. Controversially, a marked rise in serum Calcium, Potassium Ion (K+) and Cluster of Differentiation 4 (CD4) levels besides renal Glutathione (GSH), Catalase (CAT) and Superoxide Dismutase (SOD) values. Similarly, the histopathological findings confirmed the biochemical ones as the CEE restored the Oxaliplatin®-induced histological degenerations. Conclusion: In conclusion, CEE exhibited nephron-protection efficiency against Oxaliplatin®-induced nephrotoxicity; this promising effect may be achieved through the antioxidant and radical scavenging activities of its constituents.