Background: Oxidative stress is known to be a key factor in several diseases and was reported as a result of radiation exposure in human and experimental animals. Royal jelly contains free amino acids, proteins, sugars, fatty acids, minerals, and vitamins, which are reported as a preventive treatment of a wide range of disorders. Aim: The present study was designed to determine the possible protective effects of royal jelly against gamma (γ-) radiation-induced oxidative stress in male rats. Materials and Methods: Thirty two rats were divided into four groups (n=8), control, treated (rats were administrated by RJ (250 mg/kg/day) by stomach tube for 15 days, irradiated (rats were exposed to (10 Gy) whole body gamma radiations as a fractionated dose (2Gy X 5 times), treated irradiated, (rats were administrated by RJ (250 mg/kg/day) by stomach tube for 15 days before exposure to whole body gamma irradiation (10 Gy) as a fractionated dose (2X5). Serum reduced glutathione (GSH) content, superoxide dismutase (SOD) activity and lipid peroxide [malondialdehyde (MDA)] levels were assessed as well as serum total cholesterol (TC), triglyceride (TG), High density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), creatinine kinase-MB (CK-MB) and cardiac troponin I (cTnI). Also, histopathologic and histochemical changes were assessed. Results: The results showed that, GSH content, SOD activity and HDL-C were highly significantly decreased, while there was marked highly significant increase in MDA, TC, TG, LDL-C, CK-MB and cTnI due to irradiation. Numerous histopathologic changes were detected in the heart tissue of rats of the irradiated group with altered cardiac muscle fibres of the radiation-exposed group. These changes manifested good amelioration in the exposed groups that supplemented with RJ (250 mg/kg/day). Conclusion: Royal jelly has a beneficial role in reducing oxidative stress and cardio-toxicity induced by radiation exposure.