Ionizing radiation (IR) has been extensively used in industry and radiotherapy, but IR exposure from nuclear or radiological accidents often causes serious health effects in an exposed individual, and its application in radiotherapy inevitably brings undesirable damage to normal tissues. In this work, we have developed ultrathin twodimensional (2D) niobium carbide (Nb 2 C) MXene as a radioprotectant and explored its application in scavenging free radicals against IR. The 2D Nb 2 C MXene features intriguing antioxidant properties in effectively eliminating hydrogen peroxide (H 2 O 2 ), hydroxyl radicals ( • OH), and superoxide radicals (O 2•− ). Pretreatment with biocompatible polyvinylpyrrolidone (PVP)-functionalized Nb 2 C nanosheets (Nb 2 C-PVP NSs) significantly reduces IR-induced production of reactive oxygen species (ROS), resulting in enhanced cell viability in vitro. A single intravenous injection of Nb 2 C-PVP significantly enhances the survival rate of 5 and 6.5 Gy irradiated mice to 100% and 81.25%, respectively, and significantly increases bone marrow mononuclear cells after IR. Critically, Nb 2 C-PVP reverses the damage of the hematopoietic system in irradiated mice. Single administration of Nb 2 C-PVP significantly increases superoxide dismutase (SOD) activities, decreases malondialdehyde levels, and thereby reduces IR-induced pathological damage in the testis, small intestine, lung, and liver of 5 Gy irradiated mice. Importantly, Nb 2 C-PVP is almost completely eliminated from the mouse body on day 14 post treatment, and no obvious toxicities are observed during the 30-day post treatment period. Our study pioneers the application of 2D MXenes with intrinsic radioprotective nature in vivo.