This article aims to provide a research update on nitroxide radical compounds for application of anti-oxidative stress therapy. Nitroxide compounds such as 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO) can catalytically react with reactive oxygen species (ROS) and are anticipated as new anti-oxidant therapies for several diseases. However, low-molecular-weight nitroxide compounds pose several problems such as nonspecific dispersion in normal tissues, preferential renal clearance and rapid reduction of the nitroxide radical to the corresponding hydroxylamine. Nitroxide radical compounds are also known to show dose-related antihypertensive action accompanied by reflex tachycardia, increased skin temperature, and seizures. The author has recently designed novel nanoparticles, which possess nitroxide radicals in the core for novel bioimaging and nanotherapy. Nitroxide radical-containing nanoparticles (RNP) shows high safety, long blood circulation, magnetic resonance imaging and ESR imaging sensitive character and efficient therapeutic effects to several diseases such as cerebral and renal ischemia reperfusions, ulcerative colitis and Alzheimer's disease models. RNPs are, thus, promising as new nanotherapeutic materials.