Premature ovarian failure (POF) is a cessation of ovarian function in women under 40 years of age. Ovarian atrophy leads to a reduced follicle reserve, which leads to menstrual irregularities, ovarian dysfunction, and infertility. The beneficial effects of curcumin (CRC) and hesperidin (HSP) on Cyclophosphamide –induced Premature ovarian failure (POF) in a rat model were studied. POF was induced by intraperitoneal (i.p) injection of cyclophosphamide (200 mg/kg b.wt) at day one, and then (8 mg/kg b.wt/day) for the following 14 days. Two weeks after POF induction, treatment with CRC (100 mg/kg b.wt/day, i.p) and HSP (80 mg/kg b.wt/day, i.p) were started and continued for 14 days. Ninety female rats were divided into six equal groups. Group 1( Control normal group) rats received no drugs, Group 2 (POF-induced group), Group 3 (POF + CRC treated), Group 4 ( POF + HSP treated), Group5 ( POF + CRC+HSP treated) and Group 6 (Normal+CRC+HSP treated). Serum follicle-stimulating hormone (FSH) and ovarian tissues Malonedialdehyde (MDA) concentrations were significantly increased while serum estradiol (E2) level, ovarian superoxide dismutase (SOD) activity and reduced glutathione (GSH) concentration were markedly decreased in POF group as compared with control group. However, a significant increase in serum E2 , ovarian tissues SOD activity and GSH level and marked decrease in FSH and MDA concentrations were observed in rats treated with CRC or/and HSP compared with the POF group. Conclusively, curcumin and hesperidin provided an effective treatment for Premature ovarian failure induced by Cyclophosphamide in rats.