Water-soluble fullerene derivatives have often been used as effective scavengers for reactive oxygen species. Three amphiphilic amino acid C 60 derivatives, β-alanine C 60 derivative, cystine C 60 derivative and arginine C 60 derivative have been synthesized and characterized. Because of the hydrophobic interaction, the amino acid C 60 derivatives could self-assemble to form spherical aggregates. Moreover, the cystine C 60 derivative and arginine C 60 derivative could further form multilayer vesicles because of hydrogen bonding. Experiments demonstrate that the aggregate morphology could impact the protective effect of amino acid C 60 derivatives on apoptosis. These compounds were able to penetrate the cell membrane and reduce the accumulation of reactive oxygen species and cellular damage caused by hydrogen peroxide in PC12 cells. The results suggest that amino acid C 60 derivatives have the potential to prevent oxidative stress-induced cell death without evident toxicity. Hence, we hypothesize that the protective effect of amino acid C 60 derivatives on hydrogen peroxide induced apoptosis is related to many factors, such as scavenger activity and morphology of the aggregate.