Radiation therapy is one of the most effective treatments for approximately 60% of patients with cancer. During radiation exposure, the overproduction of reactive oxygen species (ROS) disrupts the lipid layer of the membrane, leading to subsequent peroxide radical formation. Cimetidine (Cim) and famotidine (Fam) are histamine H2 receptor antagonists (H2 blocker), also known as peptic ulcer drugs, that exert radioprotective effects. Vitamin C (Vit.C) is an effective free radical and ROS scavenger with significant radioprotective effects. In this experimental study, male mice (6-8 weeks and 28 ± 3 g) were used in five groups. To evaluate ionizing radiation, gamma rays were used at two doses of 2 and 4 Gy and different doses of Cim, Fam, and Vit.C administered as the protectives. Finally, the livers of the mice were isolated and homogenized. The levels of lipid peroxidase and reduced and oxidized glutathione were measured using standard methods. With increasing radiation dose, lipid peroxidase activity, GSSG level, and glutathione content increased. The findings showed that in the drug-only group, Vit.C had better protection than the other two drugs, and the combination of the three drugs had excellent radiation protection. Radiation protection of normal cells in radiotherapy is a valuable necessity. A number of drugs can protect cells against ionizing radiation through different mechanisms. The results suggest that Fam, Cim, and Vit.C can be radioprotective individually or in combination.