The present study deals with the protective effect of Spinacia oleracea L. against radiation-induced oxidative stress, which is evaluated in terms of lipid peroxidation (LPO) product and tissue levels of glutathione. Swiss albino male mice aged 6-8 weeks, weighing 22+/-3 g, each were selected from an inbred colony and divided into four groups. One group served as normal and a second group (extract of S. oleracea L. (SE) treated un-irradiated) were administered methanolic (50%) SE at a dose of 1100mg/kg body wt./day dissolved in distilled water. A third group (untreated-irradiated) was administered distilled water orally, which served as control. A fourth group (SE pre-treated irradiated) was administered methanolic (50%) SE at a dose of 1100 mg/kg body wt./day dissolved in distilled water. Two groups, one untreated-irradiated and another S. oleracea pre-treated irradiated were exposed to 5 Gy of gamma radiation at a rate of 1.07 Gy/min with a source-to-surface distance of 77.5 cm. The animals were autopsied at 1, 3, 7, 15, and 30 days post-exposure. LPO increased after irradiation up to day 15 in the untreated-irradiated group and up to day 7 in SE pre-treated irradiated mice. LPO values were significantly lower in the SE pre-treated irradiated group as compared to their respective untreated-irradiated group at all intervals, which reached normal values from day 7 onward. The percentage of protection observed in the SE pre-treated irradiated group was, 22.22%, 24.8%, 33.25%, 42.84% and 26.36% at 1, 3, 7, 15, 30 days post-exposure, respectively. Radiation-induced glutathione depletion was checked after 7 days' exposure in SE pre-treated irradiated as compared to untreated-irradiated in which recovery started after day 15. Values were significantly higher in the SE pre-treated irradiated group from their respective untreated-irradiated group at all intervals. The percentage of protection observed in the SE pre-treated irradiated group was, 29.41%, 42.68%, 43.55%, 53.81%, 39.28% at 1, 3, 7, 15, 30 days post-exposure, respectively. It is found that radiation-induced augmentation in malondialdehyde contents and depletion in glutathione changes in liver can be altered by S. oleracea L. The protection may be attributed to the combined effects of its constituents rather than to any single factor as the leaves are rich in carotenoid content (beta-carotene, lutein, Zeaxanthine), ascorbic acid, flavonoids and p-coumaric acid. Thus Spinacia, showing protection in liver, may prove promising as a rich source of antioxidants because its use is cost-effective, especially for peoples in adverse and hazardous circumstances who are living in poverty.