Background: Radioprotective efficacy of Prunus avium fruit extract (PAE) rich in vitamin A, C, E and anthocyanin was studied against radiation induced biochemical alterations in mice brain. Materials and Methods: In-vitro assays were performed with PAE for its antioxidant studies thereafter for in-vivo study, Swiss albino mice were divided into five groups. Group 1 (control) normal mice. Group 2 (PAE treated) PAE supplemented (450 mg/kg. b.wt/day) for 15 days. Group 3 (Irradiated) 5 Gy gamma-radiation treated. Group 4 (PAE + Irradiated) was administered PAE once daily for 15 consecutive days, thereafter exposed to 5 Gy gamma-radiation. Group 5 (Irradiated + PAE) was exposed to 5 Gy gamma-radiation than PAE was administered for 15 consecutive days. Brains were removed at various post treatment intervals for biochemical estimations. Results: The IC50 values of PAE for 2,2-diphenyl-1-picrylhydrazyl (DPPH·] scavenging assays, superoxide radical scavenging assays, inhibition of in vitro lipid peroxidation assays and protein carbonyl formation assay were 413 µg/ml, 7.63 µg/ml, 136.18 µg/ml and 16.94 µg/ml respectively. Furthermore the total phenolic content in PAE was equivalent to 8.38 mg/ml of gallic acid. The rate of ·OH radical scavenging activity of PAE was 0.57 times slower than SCN- derived from nanosecond pulse radiolysis studies. In-vivo study also showed that radiation (5 Gy) induced augmentation in the levels of lipid peroxidation and depletion in glutathione and protein level in mice brain were significantly ameliorated by PAE pre/post treatment. Conclusion: Results suggest that the radioprotective efficacy of PAE may be due its antioxidant property.