Oxidative stress reflects an excessive accumulation of reactive oxygen species (ROS) and is a hallmark of several acute and chronic human pathologies. Although many antioxidants have been investigated, most have demonstrated poor efficacy in clinical trials. Here we discuss the limitations of current antioxidants and describe a new class of nanoparticle antioxidants, poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs). PEG-HCCs show high capacity to annihilate ROS such as superoxide (O2(•-)) and the hydroxyl (HO(•)) radical, show no reactivity toward the nitric oxide radical (NO(•)), and can be functionalized with targeting moieties without loss of activity. Given these properties, we propose that PEG-HCCs offer an exciting new area of study for the treatment of numerous ROS-induced human pathologies..