Exposure to ionizing radiation(IR) such as abdominal and pelvic radiotherapy can result in severe intestinal injury, which is alleviated by Ginsenosides(GS) and Ginsenophenolic acids(GPAs). After treatment of IEC6 cells with IR, the growth of the cells was inhibited and the cleavage of Caspase 3 was induced, which was accompanied by the cleavage of Gasdermin E (GSDME), leading to cell apoptosis and pyroptosis. In addition, after adding caspase-3 inhibitor, the indexes of apoptosis and pyroptosis were decreased, indicating that caspase 3-dependent cleavage of GSDME promotes the apoptosis and pyroptosis of IEC6 cells. The IEC6 cells were treated with GS,GPAs and GPS before IR, and the results showed that GS and GPAs could repair the apoptosis and pyroptosis , and alleviate the increase of ROS caused by IR. Moreover, the addition of GS or GPAs can promote cell proliferation. These results suggest that IR induces apoptosis and GSDME-dependent pyroptosis through Caspase 3 activation, which can be relieved by GS and GPAs, thus supporting the potential of GS and GPAs as prevention and treatment of IR-induced intestinal injury.