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Human exposure to ionizing radiation induced overproduction of free radicals leading to oxidative stress. This study aims to evaluate the possibility of using of coffee and cardamom mixture, as natural antioxidant compounds, to ameliorate the damage effect of oxidative stress. Phenolic contents in coffee and essential oils in cardamom were identified by using HPLC chromatography and GC/MS analysis. Four groups of adult male rats were used; the control group (A), the second group (B) received orally mixture extract of coffee and cardamom (60 mg/100g body weight) for 8 weeks, the third group (C) γ-irradiated (6 GY) and the fourth group (D) received orally mixture extract for 8 weeks and exposed to γ-irradiation at the 4th week. The results revealed that the administration of mixture extract of coffee and cardamom were significantly reduced the damage effect induced by γ-irradiation exposure. Accordingly, it could be concluded that, via the adjustment of the antioxidant status, decreasing the releasing of lipid peroxides and the subsequent amending of different biochemical parameters and some hormones, mixture of coffee and cardamom could ameliorate the hazardous effects of oxidative stress induced by irradiation exposure.