This study used radiation-induced damage in Wistar albino rats as a proxy for assessing the radio and antioxidant protective efficacy of diosmin-hesperidin, a natural plant citrus flavone of hesperidin derivative. Before being exposed to a cumulative dose (10Gy) of gamma radiation in the form of fractionated dose (2 Gy for 5 times every other day), rats were given diosmin-hesperidin dose (200 and 100 mg/kg body wt. correspondingly) orally for a month (every other day). The purpose of this study is to assess the diosmin-hesperidin combination's radioprotective and antioxidant efficacy. Apoptosis was evaluated using several methods, including real-time polymerase chain reaction (RT-PCR) analysis, biochemical analysis, histopathological changes, the comet assay, and caspase-3 activity. As shown by the findings, pretreatment with diosmin+hesperidine counteracted the detrimental effects of radiation on antioxidant indices (SOD, GPx, and GSH), lipid peroxidation, DNA damage, and apoptosis. Lipid peroxidation, DNA damage, and tissue damage were all mitigated by a diosmin+hesperidine dose (200 and 100 mg/kg body wt., respectively) that brought antioxidant status back to near normal. Histopathological analyses corroborated these findings, demonstrating that the livers of albino rats were protected from gamma-irradiation-induced damage when diosmin+hesperidine was given prior to the radiation exposure. So, the evidence suggests that diosmin+hesperidine can protect rats from radiation-induced harm. In addition, there were no signs of metabolic changes or DNA damage in the diosmin+hesperidine pretreatment group.