Plant extracts with antioxidant activities have shown nephroprotection against IR injury. Jatropha dioica (Jd) possesses antioxidant activity. Our aim was to evaluate the effects of a hydroalcoholic Jd extract against IR injury in Wistar rats. Rats were divided into groups (n = 6): sham (SH); no toxicity (JdTox; 300 mg/kg/day of extract for 7 days); IR (on day 7 [I: 45 min/R: 24 h]); and Jd+IR (same treatment as JdTox; same surgical procedure as IR). AST and LDH were significantly lower in the JdTox. IR exhibited significantly higher CrS, BUN, and MDA compared with SH; Jd+IR showed reductions in these markers. GSH and SOD levels were significantly lower in IR compared with SH; an increase in these markers was observed in the Jd+IR. Histologically, IR showed significant increases in medullary tubular necrosis, medullary protein casts, and medullary vascular congestion compared with SH and JdTox. In Jd+IR, a significant decrease was observed only in medullary tubular necrosis. Therefore, the evaluated hydroalcoholic Jd extract dose showed no nephrotoxicity and hepatotoxicity. Jd extract pretreatment attenuated IR-induced renal injury, as evidenced by the improved serum markers of renal damage and oxidative stress.