Protein amyloidosis is related to many neurological disorders. Nanoparticles (NPs) due to their small size have the potential to modulate the protein monomers/oligomers assembly into fibril forms, as well as the disaggregation of preformed fibrils. Herein, we have synthesized ZnO nanoflowers and polyol-coated ZnO NPs of relatively small size (40 nm) with cylindrical shape, through solvothermal and microwave-assisted routes. The effect of the different morphology of nanostructures on the fibrillation/antifibrillation process was monitored in bovine serum albumin (BSA) and human insulin (HI) by fluorescence Thioflavin T (ThT) measurements. Although both nanomaterials affected the amyloid formation mechanism as well as their disaggregation, ZnO nanoflowers with their sharp edges exhibited the greatest amyloid degradation rate in both model proteins (73% and 35%, respectively) and inhibited the most the insulin fibril growth, while restrained also the fibrillation process in the case of albumin solution. In order to explain the described in vitro activity of ZnO nanostructures, we adopted in silico molecular docking studies on the crystal structure of BSA and HI. The binding energy of ZnO NPs was found lower for BSA (-5.44), highlighting their ability to act as catalysts in the fibrillation process of albumin monomers.