Sesamol (3,4-methylene dioxyphenol) protected mice from adverse effects of whole body gamma-irradiation. Studies indicated that oral administration of sesamol (SM), 1 hour prior to whole body gamma-irradiation (2–6 Gy), significantly protected cellular DNA in various tissues of mice, as evident from alkaline comet assay. Whole body exposure of mice to a sub-lethal dose of 6 Gy gamma radiation resulted in oxidative damage in various tissues of mice, and radiation-induced peroxidative damage and depletion of antioxidants such as GSH, GPx in tissues such as liver, kidney and brain. Administration of SM prior to radiation exposure resulted in prevention of radiation-induced peroxidation of membrane lipids and depletion of cellular antioxidants in these tissues. The administration of SM significantly reduced the mortality of the animals following exposure to a lethal dose of 10 Gy whole body gamma-radiation and improved the recovery of the body weight. Thus the studies suggest that oral administration of SM could offer protection to mice from the deleterious effects of ionising radiation.