Introduction: Tribulus terrestris L. (TTL) is an annual plant of the family Zygophyllaceae that has been used for many diseases including urinary tract diseases. The fruits and roots of TTL have been used as a folk medicine for thousands of years in Mongolia, China, Iraq, India, Sudan and Pakistan. Numerous bioactive phytochemicals, such as saponins, flavonoids, alkaloids and glycosides, have been isolated and identified from TTL that are responsible alone or in combination for various pharmacological activities. However, to date, the nephroprotective effects of TTL on cisplatin-induced animal models have not been investigated. Purpose: The present work aimed to investigate the protective effects of different doses of Tribulus terrestris L. (TTL) against cisplatin-induced nephrotoxicity in mice. Materials and methods: The renal injury was modeled by intraperitoneal injection of cisplatin for 5 consecutive days (5 mg/kg). Nephroprotection of TTL was investigated by oral administration of different doses of TTL aqueous extract at a daily dose of 20 mg/kg and 40 mg/kg for 14 consecutive days, starting 7 days prior to cisplatin administration. Results: We demonstrated that pretreatment with different doses of TTL aqueous extract significantly reduced blood urea nitrogen (BUN) and serum creatinine (Cr) levels and histophatological changes observed in cisplatin-administrated mice. Conclusion These data suggested that TTL might be a potential candidate for neoadjuvant chemotherapy of cisplatin. The dose of TTL 40 mg/kg was the most effective.