Background: Nandrolone-decanoate (ND); is an anabolic steroid. Its toxic effects on the heart as arrhythmias, acute myocardial infarction, and sudden death have been recorded. Moringa oleifera extract (MOE); is a herbal extract used to treat various diseases due to its antioxidant effect. Aim; This study was designed to evaluate the efficacy of MOE as a protective agent against cardiotoxicity induced by ND. Material and methods; Thirty-two adult male albino rats were allocated into four groups. Control group; MOE treated group; rats were given MOE by oral gavage (400 mg/kg/day) for four weeks. ND group; rats were injected ND S.C; at a dose of 20 mg/kg/week for four weeks. ND+MOE-treated group; rats simultaneously administrated ND; (20mg/kg/week S.C.) with MOE (400 mg/kg/day by oral gavage) for four weeks. Serum levels of cardiac enzymes were estimated. Also; MDA, GSH, SOD, IL-6, TNF- α, and IL-10 levels in cardiac tissue were estimated. Cardiac samples were processed to light, an immune-histochemical study using anti-P53 and anti-CX43 antibodies as well as electron microscopic examination. Morphometric; and statistical studies were done. Results; In the ND group, serum levels of cardiac biomarkers and cardiac tissue levels of MDA, TNF-α, and IL-6 were significantly increased with significant diminution in the activity of catalase, SOD, diminished GSH, and IL-10 in the cardiac tissues. Light; microscopic examination showed wide endomysium, inflammatory cell infiltration, and lacerated and wavy cardiac muscle fibres were observed. There was a marked deposition of collagen fibres at areas of interrupted muscle fibres. Positive; P53 immuno-expression in the nuclei and decreased expression of CX43 were observed. Ultra-structurally; interrupted myofibrils, dilated sarcoplasmic reticulum, and a disorganized intercalated disc was observed. In (ND+MOE) group; showed marked amelioration in the cardiac architecture and ultrastructure, down-regulation of P53, and CX43 immuno-expressions, and a significant reduction in serum level of cardiac biomarkers, and cardiac tissue levels of MDA, TNF-α and IL-6 with a significant increase in activity of catalase, SOD, diminished GSH and IL-10 in the cardiac tissues. Conclusion; MOE could alleviate the cardio-toxic effects induced by ND in rats through anti-inflammatory, anti-oxidant; and anti-apoptotic effects.