Abstract: Cisplatin (cis-dichlorodiamineplatinum II) is a potent antineoplastic agent against several types of tumor. Nevertheless, its clinical utility is limited due to its cytotoxic adverse effects that include nephrotoxicity. Several factors including inflammation, oxidative stress, DNA damage and mitochondrial injury are involved in cisplatin-induced cell injury. Nigella sativa and vitamin E possess the anti-inflammatory and antioxidant properties. Accordingly, the present study was designed to investigate the protective effects of hydroalcoholic extract of Nigella sativa seeds and vitamin E on cisplatin-induced nephrotoxicity. Forty eight male Wistar rats were randomly divided into 8 groups and treated daily with Nigella sativa extract (100 or 200 mg kg–1, i.p.) or vitamin E (100 mg kg–1, i.p.) 1 h before single dose cisplatin injection (6 mg kg–1, i.p.) and continued for 5 days. Serum and urinary biochemical parameters were measured on day 0 and 6. Histopathological examination of the kidney and determining the kidney index were performed on day 6. The results showed that serum urea and creatinine concentrations, as well as urine glucose, kidney index and histopathological damage were significantly increased in cisplatin group compared with control group, while Glomerular Filtration Rate (GFR) and urea clearance were significantly reduced. Similar alterations in biochemical factors were observed in groups that received cisplatin together with Nigella sativa extract or vitamin E compared to control group. However, treatment with Nigella sativa extract or vitamin E could improve histopathological damages due to cisplatin. In conclusion, Nigella sativa extract or vitamin E treatment attenuated the histological alterations induced by cisplatin.