Fullerene (C60) has been regarded as an effective radical scavenger for many years, but the highly hydrophobic nature strongly limits its application in biological fields. Herein, a simple and green strategy for synthesizing water-soluble fullerene derivative was reported, in which intrinsic C60 was grafted by amine oxide functional group (AO-C60). In addition to its excellent aqueous dispersion, AO-C60 exhibited extremely low toxicity to mice macrophage cell RAW264.7. Further experiments have confirmed the prominent antioxidative ability of AO-C60 towards typical free radicals including 1,1-diphenyl-2-picrylhydrazy (DPPH) radical, hydroxyl radical (•OH) and nitric oxide (•NO) without the help of metal loading, while the IC50 could be as low as 0.09 mg/mL. Our work will shed light on the development of anti-oxidative nanoagents with both effectiveness and bio-safety. [ABSTRACT FROM AUTHOR]