In the present study we investigated the radioprotective activity of hydroalcoholic leaf extracts of Psidium guajava (P.G) against rats exposed to X rays. Exposure to ionizing radiation like X rays induces oxidative damage in normal tissues leading to their death or transforming them into cancerous tissues. To study the optimum dose of radioprotection, rats were administered with different doses (50,100,200,400 mg/kg body weight) of Psidium guajava leaf extracts daily for five consecutive days. One hour after last administration of leaf extracts the rats were treated with 6.6 Gy of x rays.200 mg/kg body weight was selected as an optimum dose for radioprotection based on survival analysis. Pretreatment of 200 mg/kg body weight of P.G leaf extract increased the levels of antioxidant enzymes such as superoxide dismutase, catalase, reduced glutathione and lowered the levels of lipid peroxidation, protein carbonyls and nitric oxide when compared to irradiated group in liver tissue homogenates. DNA damage indicators analyzed through comet assay showed a reduction in Olive tail movement and percentage DNA in tail significantly in P.G pretreated group when compared to irradiated group alone. Pretreatment of P.G leaf extract at a dose of 200mg/kg body weight protected cells from apoptosis which was analyzed microscopically by Ethidium bromide /Acridine orange staining. Our findings demonstrate the role of P.G leaf extract as a radio modulator in vivo, consequent to its powerful antioxidant activity in vitro and could be beneficial in combating radiation induced damage in living systems.