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Protein misfolding and subsequent aggregation into insoluble amyloid deposits are associated with various diseases, including Alzheimer's disease, systemic amyloidosis, and type 2 diabetes mellitus (T2DM). In T2DM, the peptide hormone islet amyloid polypeptide (IAPP), which regulates glucose homeostasis, aggregates in the pancreas, forming soluble cytotoxic aggregates and amyloid fibrils that contribute to ß-cell dysfunction and death. Thus, the inhibition of IAPP aggregation consists of a promising strategy for treating T2DM. Natural gallotannins are potential amyloid modulators, though their effects on amyloid self-assembly are not fully understood. This study examines two gallotannins, 1,3,6-tri-O-galloyl-ß-d-glucose (ß-TGG) and corilagin, and their inhibitory effects on IAPP aggregation. Using thioflavin T fluorescence, atomic force microscopy, and circular dichroism, it was found that the gallotannins delay IAPP self-assembly and reduce the length and quantity of amyloid fibrils. Despite structural similarity, corilagin exhibited markedly higher antiaggregative activity at lower concentrations compared to ß-TGG. Peptide monomer-gallotannin interactions were further investigated using all-atom explicit solvent molecular dynamics simulations, providing valuable insight into the binding of both gallotannins to monomeric IAPP. Furthermore, corilagin provided significant cytoprotective effects against IAPP-induced cytotoxicity and membrane damage in pancreatic ß-cells. Mechanistic analysis revealed that corilagin exerts its effects primarily by inhibiting secondary nucleation and facilitating off-pathway aggregation into cytocompatible proteospecies. Together, these findings highlight the potential of both gallotannins in inhibiting amyloid self-assembly and inspiring the development of antiaggregative agents.