Premature ovarian failure (POF) is a cessation of ovarian function in women less than 40 years old. The atrophy of the ovary leads to decreased follicle storage, which leads to irregular of the menstrual cycle, dysfunction of the ovary and causes infertility. The current study was conducted to investigate the effects of curcumin (CRC) and hesperidin (HSP) on POF in a female rat. POF was Caused by intraperitoneal (i. p.) injection of cyclophosphamide (200 mg/kg b. wt.) at the first day and then (8 mg/kg b. wt./day) for the next 14 days. The treatment with CRC (100 mg/kg b. wt./day, i. p) and / or HSP (80 mg/kg b. wt./day, i. p.) were started and continued for 14 days after two weeks for POF induction. Ninety female rats were classified into six groups. Group 1 (Control), Group 2 (POF-induced), Group 3 (POF+ CRC), Group 4 (POF+HSP), Group 5 (POF+CRC+HSP) and Group 6 (Normal+CRC+HSP). Serum follicle-stimulating hormone (FSH) and ovarian tissues malondialdehyde (MDA) concentrations significantly increased, while serum estradiol (E2) level, ovarian tissues reduced glutathione (GSH) and superoxide dismutase (SOD) markedly decreased in POF group as compared with the control group. However, the 3 rd , the 4 th and the 5 th treated groups had a significant increase in serum E2, ovarian tissues SOD activity and GSH level and marked decrease in FSH and MDA concentrations compared with the POF group. The histopathological changes in the three treated groups improved toward control group. Conclusively, Hesperidin superior to curcumin in the alleviation of oxidative stress and hormonal alterations in a rat model of cyclophosphamide-induced premature ovarian failure.