Context:Radiation therapy is the prime treatment modality against various cancers. However, its use is limited due to the effects of radiation on normal tissues.Aims:In view of this, present study was carried out to evaluate the radioprotective potential of Rutin (RUT) and Quercetin (QRT) in Swiss Albino mice exposed to the whole body gamma radiation. To gain insight into the mechanism of action, RUT and QRT were tested for its antioxidant levels in mice.Settings and Designs:Optimum protective dose of RUT and QRT against radiation induced animal mortality was selected by administration of various doses of the RUT and QRT before 10 Gy gamma irradiation.Materials and Methods:Swiss Albino mice were used for the assessment of radiation induced sickness along with the survival analysis and anti-oxidative properties of RUT and QRT.Statistical Analysis Used:Survival studies were determined using the Kaplan-Meier survival curves.Results:The maximum survival was observed with 10 mg/kg. b. wt. and 20 mg/kg. b. wt. of RUT and QRT respectively, this dose was considered as an optimal dose for radioprotection. Treatment of mice with RUT and QRT before irradiation delayed the onset of mortality as compared with the untreated irradiated controls. The oral administration of RUT and QRT resulted in an increase in the radiation tolerance and the dose reduction factor was found to be 1.15 and 1.11 respectively. RUT and QRT pre-treatment significantly (P < 0.01) elevated levels of reduced glutathione, glutathione-S-transferase, catalase, Superoxide dismutase, and a decreased lipid peroxidation in mouse liver homogenate at 24 h after exposure to 4.5 Gy.Conclusions:Present findings demonstrate the potential of RUT and QRT in mitigating radiation-induced mortality, which may be attributed to the elevation in the antioxidant status, anti-lipid peroxidative potential.