Abnormal peptide assembly and aggregation is associated with an array of neurodegenerative diseases including Alzheimer's disease (AD). A detailed understanding of how nanostructured materials such as oxidized graphene perturb the peptide assembly and subsequently induce fibril dissociation may open new directions for the development of potential AD treatments. Here, we investigate the impact of surface inhomogeneity of graphene oxide (GO) on the assembly of amyloid-beta Aβ16-21 peptides on GO surfaces with different degrees of oxidation using molecular dynamics simulations. Interestingly, nonuniform GO nanosheets (in terms of oxidation sites) have a much stronger perturbation effect on the structure of Aβ16-21 assembly. The Aβ peptides exhibit a remarkable tendency in binding to the scattered interfaces between unoxidized and oxidized regions, which induces the dissociation of Aβ amyloid fibril. These findings should deepen our understanding of surface-induced peptide dissociation and stimulate discovery of alternative AD treatments.