Radiation colitis is an inflammatory response induced by damage to colonic tissue from radiation therapy that primarily affects patients undergoing abdominal or pelvic radiation treatments. In this study, we designed a selenium-loaded probiotic (EcN-Se@SA) encapsulated in sodium alginate gel for the oral treatment of radiation colitis. Selenium nanoparticles (Se NPs) exhibit antioxidant, anti-inflammatory, ferroptosis, and tissue repair-promoting properties. To enhance the therapeutic efficacy of Se NPs for radiation-induced colitis, we combined Se NPs with Escherichia coli Nissle 1917 and encapsulated them in sodium alginate hydrogel. The resulting EcN-Se@SA formulation not only withstands gastric acid and intestinal fluids but also remains in the colon and cecum for extended periods. Oral administration of EcN-Se@SA attenuates X-ray-induced colitis in mice through its antioxidant and anti-inflammatory effects, macrophage reprogramming, and inhibition of ferroptosis in histiocytes. This work introduces a promising therapeutic candidate for the treatment of radiation colitis.