The pathology Alzheimer’s disease (AD) is associated with the self-assembly of amyloid-β (Aβ) peptides into β-sheet enriched fibrillar aggregates. A promising treatment strategy is focused on the inhibition of amyloid fibrillization of Aβ peptide. Fullerene C60#nbsp;is proved to effectively inhibit Aβ fibrillation while the poor water-solubility restricts its use as a biomedicine agent. In this work, we examined the interaction of fullerene C60#nbsp;and water-soluble fullerenol C60(OH)6/C60(OH)12#nbsp;(C60#nbsp;carrying 6/12 hydroxyl groups) with preformed Aβ40/42#nbsp;protofibrils by multiple molecular dynamics simulations. We found that when binding to the Aβ42#nbsp;protofibril, C60, C60(OH)6#nbsp;and C60(OH)12#nbsp;exhibit distinct binding dynamics, binding sites and peptide interaction. The increased number of hydroxyl groups C60#nbsp;carries leads to slower binding dynamics and weaker binding strength. Binding free energy analysis demonstrates that the C60/C60(OH)6#nbsp;molecule primarily binds to the C-terminal residues 31-41, whereas C60(OH)12#nbsp;favors to bind to N-terminal residues 4-14. The hydrophobic interaction plays a critical role in the interplay between Aβ and all the three nanoparticles, and the π-stacking interaction gets weakened as C60#nbsp;carries more hydroxyls. In addition, the C60(OH)6#nbsp;molecule has high affinity to form hydrogen bonds with protein backbones. The binding behaviors of C60/C60(OH)6/C60(OH)12#nbsp;to the Aβ40#nbsp;protofibril resemble with those to Aβ42. Our work provides a detailed picture of fullerene/fullerenols binding to Aβ protofibril, and is helpful to understand the underlying inhibitory mechanism.