Cyclophosphamide (CP) is an alkylating operator generally utilized as an anti-neoplastic medication, documented to instigate joined cardio-hepatic injury as one of its side effects. Ellagic acid (EA) is Polyphenolic plant compound presents in the organic products. EA is partially responsible for their useful health properties on oxidation-related diseases. Aim: This experiment was intended to assess the conceivable defensive impacts of Ellagic Acid (EA) against cyclophosphamide (CP)- initiated cardio-hepatic injury in rats. Material and methods: Twenty four male albino rat were divided to four equivalent groups: control one: got standard eating routine; EA group: got EA (60 mg/kg B.W / intraperitoneal, day by day for four weeks), the CP-treated one (200 mg/kg B.W /intraperitoneal, as a solitary dose), and the CP+ EA group. The study duration was four progressive weeks. Laparotomy was finished with heart and liver tissues' extraction and processing for histopathological assessment and immune-histochemical study for caspase-3. We additionally surveyed the oxidative enzymatic and lipid peroxidation biochemical profiles. Results: We observed that EA restored the cardio-hepatic histopathological damage induced by CP and significantly reduced the apoptotic marker (caspase -3) up regulation. A rescue to control levels was likewise obvious in the EA+CP-treated animals, as in regards to the oxidative enzymatic action and lipid peroxidation profiles. Conclusion: EA might display perceptible anti-oxidant and anti-apoptotic effects on the cardio-hepatic cytological, morphological and immune-histochemical changes actuated by CP. EA is proposed to be a potential contender to improve the cardio-hepatic toxicity and can be considered clinically after suitable clinical evaluation.