Radiation-induced injury is a key factor in determining the prognosis of patients undergoing radiotherapy, highlighting the significant clinical importance of developing drugs for radiation prevention and treatment. Especially in oncology, radiation-induced injury remains a pivotal determinant of therapeutic outcomes, because of its direct correlation with normal tissue damage during radiotherapy. Efforts to mitigate or treat such injury are thus paramount in enhancing the overall safety and efficacy of cancer treatment. Novel nanomedicines with prolonged systemic circulation, versatile drug-loading capacities, enhanced tissue retention, and stimuli responsiveness exhibit unique advantages in the treatment and prevention of radiation-induced diseases, as they can be designed based on the specific microenvironment of radiation-damaged tissues, which offers innovative solutions to address the limitations of conventional radioprotectors such as short half-life, poor tissue targeting, and systemic side effects. This review thus aims to provide an overview of recent advance in the design and application of nanomaterials for radiation prevention and treatment. Generally, ionizing radiation damages cells either by inducing DNA double-strand breaks or through the generation of reactive oxygen species (ROS). The resulting oxidative stress would disrupt the structural integrity of cell membranes, proteins, and nucleic acids, leading to apoptosis, chronic inflammation, and systemic effects across multiple systems, including hematopoietic system, gastrointestinal tract, skin, lungs, brain, and heart. Radiation protection strategies focus on scavenging ROS, stimulating cellular repair and regeneration, inducing tissue hypoxia, and inhibiting apoptotic pathways. Recent advances in nanomedicine have introduced novel approaches for targeted and efficient radiation protection and treatment. For radiation-induced hematopoietic injury, nanoparticles can been designed to promote red and white blood cell regeneration while reducing oxidative stress. To address radiation-induced gastrointestinal injuries, nanomaterials enable localized antioxidant delivery and extended intestinal retention, effectively relieving radiation enteritis by scavenging ROS and modulating gut microbiota. For radiation-induced skin injuries, self-assembling peptide hydrogels that mimic the extracellular matrix can serve as effective scaffolds for wound healing. These hydrogels exhibit excellent antioxidant properties, stimulating angiogenesis, and accelerating the recovery of radiation dermatitis. In cases of radiation-induced brain damage, nanoparticles were designed to cross the blood-brain barrier to rescue neuronal damage and protect cognitive function. This review provides an in-depth insight into the mechanisms underlying radiation-induced injuries and highlights how nanomaterial were construtced according to the specific injury. Therefore, nanotechnology endowers durgs with transformative potential for preventing and treating radiation-induced injuries. Despite significant progress in nanomedicine, there are still challenges in long-term biocompatibility, precise targeting of damaged tissues, and scalable manufacturing. In addition, an in-depth understanding of the interactions between nanomaterials and biological systems remains to be covered. Future efforts should focus on optimizing design strategies, enhancing clinical translatability, and ensuring long-term safety, ultimately improving patient outcomes. Besides, expanding research into other radiation-induced diseases, such as radiation-induced ophthalmic disorders and hepatic injuries, may diversify therapeutic options.