THIS WORK aims to study the effect of fractionated doses of Cerastes cerastes (C. cerastes) crude venom (CCV) on physiological alterations in different tissues of 5.5 Gy γ-irradiated mice. Male mice were grouped into: Control group. CCV group; mice received via inter peritoneum (i.p.) ⅓LD50 CCV in fractionated doses over a period of 2 weeks. Irradiated group; mice whole body exposed to 5.5 Gy γ-rays. Irradiated+ CCV; mice received via i.p ⅓LD50 CCV in fractionated doses over a period of 2 weeks starting 1 h post irradiation. Exposure to 5.5 Gy γ-rays elevated advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels and decreased glutathione (GSH) content of liver, spleen and kidney. Moreover, γ-irradiation significantly decreased calcium (Ca) and elevated zinc (Zn), and cupper (Cu) in liver, spleen and kidney tissues compared to the control, whereas, iron (Fe) was significantly elevated in liver and spleen and decreased in kidney. In addition, serum urea and creatinine and their ratio were significantly increased. Irradiated mice treated with fractionated CCV showed significant amelioration of oxidative stress and element alterations in the different tissues. It could be concluded that the fractionated doses of CCV (⅓LD50) might have favourable potential against irradiation induced-biochemical injuries.