Abstract: Background and Objective: Aspartame (ASP) one of the famous artificial sweeteners used as substitution of the sugar in foods and beverages. The study was aimed to investigate the oxidative responses and histopathological changes induced by ASP on the kidney of rats and the ameliorative role of L-carnitine (LC) to prevent the toxicity. Materials and Methods: Rats were split into six groups (n = 8) as follow: control, ASP (low dose, LD) (75 mg kg–1), ASP (high dose, HD) (150 mg kg–1), 10 mg kg–1 of LC, ASP-LD+LC and ASP-HD+LC, all groups treated for successive 30 days. Results: The ASP marked decreased the renal levels of reduced glutathione (GSH), activities of antioxidant enzyme markers and increased lipid peroxidation levels. DNA damage was significantly increased in ASP-LD and ASP-HD groups as compared to control animals. The LC prevented the ASP-induced kidney damage as specified by ameliorating all the above-mentioned parameters. Histopathological changes were parallel with the biochemical alternation in ASP groups. Conclusion: The renal toxicity induced by ASP in rats could be improved by LC through different protective mechanisms.