Radiation therapy has become one of the most important treatment modalities for human malignancy, but certain immediate and delayed side-effects on the normal surrounding tissues limit the amount of effective radiation that can be administered. After exposure of the abdominal region to ionizing radiation, nearly all patients experience transient symptoms of irradiation of the bowel. Acute-phase symptoms may persist for a short time, yet long-term complications can represent significant clinical conditions with high morbidity. Data from both experimental studies and clinical trials suggest the potential benefit for probiotics in radiation-induced enteritis and colitis. On the other hand, it is well evidenced that both useful and harmful effects of therapeutic applications of ionizing radiation upon living systems are ascribed to free-radical production. Therefore, the hypothesis that probiotics reinforce antioxidant defense systems of normal mucosal cells exposed to ionizing radiation may explain to an extent their beneficial action. The aim of this review is threefold: First, to make a short brief into the natural history of radiation injury to the intestinal tract. Second, to describe the primary interaction of ionizing radiation at the cellular level and demonstrate the participation of free radicals in the mechanisms of injury and, third, to try a more profound investigation into the antioxidant abilities of probiotics and prebiotics based on the available experimental and clinical data.