It is important to maintain a reactive oxygen species (ROS) balance in organisms; thus, a valid ROS scavenger with good biocompatibility is urgently required. To prepare a high-efficiency ROS scavenger, multiple ethylenediamine (EDA) groups are bonded for the first time to a metallofullerene Gd@C82 to obtain water-soluble Gd@C82-(EDA)8 nanoparticles (NPs) through a facile solid-liquid reaction. Gd@C82-(EDA)8 NPs with a relatively better conjugation possess an excellent capability to scavenge hydroxyl radicals. Moreover, Gd@C82-(EDA)8 NPs exhibited a remarkable cytoprotective effect against H2O2-induced injuries to human epidermal keratinocytes-adult (HEK-a) cells at a low concentration of 2.5 μM. In contrast, Gd@C82-(OH)26 NPs that modified with hydroxyls show an apparent protective effect at a much higher concentration of 40 μM. This outstanding cytoprotective performance of Gd@C82-(EDA)8 NPs is mainly attributed to their extremely high cellular uptake and comparably strong conjugation. Gd@C82-(EDA)8 NPs with good biocompatibility exhibit excellent ROS scavenging capability even at a significantly low concentration, which promotes its versatile applications in cosmetics and biomedicine.