The radioprotective effect of a hydroalcoholic extracted material from the fruit of Aegle marmelos (AME) was studied in mice exposed to different doses of gamma radiation. The optimum dose for radioprotection was determined by administering 0, 5, 10, 20, 40, or 80 mg/kg body weight of AME intraperitoneally (ip) once daily, consecutively for 5 days before exposure to 10 Gy of gamma radiation. A total of 20 mg/kg of AME for 5 consecutive days before irradiation was found to afford maximum protection as evidenced by the highest number of survivors after 30 days postirradiation. Animals from all groups were monitored for 30 days postirradiation for development of symptoms of radiation sickness and mortality. Treatment of mice with AME before exposure to different doses of gamma radiation reduced the severity of symptoms of radiation sickness and mortality with all exposure doses. This was accompanied by an increase in number of survivors in the AME + irradiation group when compared with the concurrent sterile physiological saline (SPS) + irradiation group. AME pretreatment protected mice against the gastrointestinal as well as bone marrow deaths, as evidenced by the greater number of survivors on day 10 or 30, respectively. LD50/30 was found to be 8.2 Gy for the SPS + irradiation group, while it was 8.8 Gy for AME + irradiation. The dose-reduction factor (DRF) was found to be 1.1 for AME + irradiation group. The acute toxicity study of AME showed that it was nontoxic up to a dose of 6 g/kg body weight, the highest drug dose that could be administered. Irradiation of animals resulted in a dose-dependent elevation in lipid peroxidation in liver, kidney, stomach, and intestine of mice. Conversely, GSH concentration declined in a dose-dependent manner. Treatment of animals with AME before irradiation caused a significant decrease in the lipid peroxidation accompanied by a significant elevation in the GSH concentration in liver, kidney, stomach, and intestine of mice determined at 31 days postirradiation.