Present investigations aimed to compare the anticancer and antioxidant activities of Sepia pharaonis ink extract (SIE) and Ellagic acid (EA) to cyclophosphamide (CP). Materials and Methods: Male Wistar Albino rats were grouped into five groups, each with ten rats. Control group (Group I) received (2 ml/kg 0.9% NaCl b.w. i.p.). Group II served as CP group was received (200 mg/kg CP b.w. i.p.). Rats of groups III, IV and V received (200 mg/kg CP b.w. i.p.) and treated with SIE (200 mg/kg b.w.), EA (60 mg/kg) and SIE (200 mg/kg b.w.) + EA (60 mg/kg), respectively. GSH, CAT, SOD, NO, and MDA levels were measured in all groups' liver and renal tissues. Histopathological examinations of the liver and kidney were performed. Results: In the liver and renal tissue homogenate of CP-treated animals, there was a highly significant reduction in GSH, CAT, and SOD, as well as a striking elevation of MDA and NO. In all treated animals with SIE, EA, and SIE+EA, however, there was a substantial decrease in liver and renal MDA and NO levels with a moderate increase in GSH, CAT, and SOD activities. After CP treatment, liver and kidney tissues showed extensive necrosis, but CP+ SIE+ EA treatment revealed regeneration of some hepatocytes and kidney cells. Conclusion: SIE and EA were both successful in reducing oxidative stress caused by CP. The effect and antitumor properties of SIE and EA as antioxidants were supported by histopathological examination in this study.