<abstract> <p>The search for potent radiation-protective drugs for clinical use continues. Studies have, so far, focused on targeting the neutralization of radiation-generated reactive oxygen species (ROS) to protect the cells against the deleterious effects of exposure to ionizing radiation. However, the development of efficacious radioprotective drugs, which are mostly low molecular weight (LMW) compounds, is mainly limited due to their inherent toxicity and rapid excretion from the body. Thus, researchers reformulated these LMW compounds into nano-based formulations. This review discusses recent advances in the use of self-assembling redox nanoparticles as a new group of radioprotective agents. The copolymer micelle (herein referred to as redox nanoparticles; RNP) contains an active part, amino-TEMPO, that effectively scavenges radiation-induced ROS in the body, as demonstrated <italic>in vivo</italic>. With the use of nanoparticle-based technologies, optimized formulations of these LMW ROS-neutralizers lead to the significant reduction of its toxicity, high bioavailability and longer blood circulation, which consequently resulted in its notable enhanced efficacy (for example, increased survival rate, reduced radiation-induced syndromes and organ damage) against the damaging effects of ionizing radiation. Consistent with the available data on the use of RNP and other nano-based radioprotective agents, it can be concluded that the inherent ROS-targeting activity of a drug intended for radiation protection is as vital as its bioavailability in the specific tissues and organs, where the short-lived ROS are produced during radiation exposure. In this review article, we summarized the current status of the development of radioprotective agents, including our self-assembling radioprotective agents.</p> </abstract>