Background: Although ionizing radiation is a risk factor, it is a therapeutic agent for cancer. Objectives: The protective and defensive effect of L-Carnitine and vitamin E on gastrointestinal tract organs (liver, spleen and intestine) post whole body gamma irradiation exposure. Material and methods: 56 male albino rats, which were divided into four groups (14 rats per group); group (I): Control group, group (II): rats were irradiated with a single dose of whole body gamma rays (6 Gy) and left 4 weeks. Group (III): rats were given L- Carnitine for five days, then irradiated by same dose. Group (IV): rats were received L- Carnitine and vitamin E for five days then irradiated by same dose. At 1 and 4 weeks post radiation exposure, seven rats from each group were scarified, blood and GIT tissue samples were collected. Results: Liver and blood samples: radiation related degenerative damage was obviously higher in the radiation group than the control group with elevated liver enzymes, however pretreatment groups revealed reduced radiation induced acute liver damage compared to the radiation group with significant improvement in liver enzymes. Spleen and intestinal samples: radiation induced damage were significantly higher in the radiation group versus the control group, however, in pre-treatment groups no significant improvement in radiation induced effects were noted compared with radiation group. Conclusion: A great radio protective effect of both L- carnitine and vitamin E after radiation exposure mainly in liver tissue and its enzymes but not in both spleen and intestinal tissue.