Natural polyphenols are one of the most actively investigated categories of amyloid inhibitors, and resveratrol has recently been reported to inhibit and remodel the human islet amyloid polypeptide (hIAPP) oligomers and fibrils. However, the exact mechanism of its action is still unknown, especially for the full-length hIAPP1-37. To this end, we performed all-atom molecular dynamics simulations for hIAPP1-37 pentamer with and without resveratrol. The obtained results show that the binding of resveratrol is able to cause remarkable conformational changes of hIAPP1-37 pentamer, in terms of secondary structures, order degree, and morphology. By clustering analysis, two possible binding sites of resveratrol on the hIAPP1-37 pentamer were found, located at the grooves of the top and bottom surfaces of β-sheet layer, respectively. After the binding free energy calculation and residue energy decomposition, it can be concluded that the bottom site is the more possible one, and that the nonpolar interactions act as the driving force for the binding of hIAPP1-37 to resveratrol. In addition, Arg11 is the most important residue for the binding of resveratrol. The full understanding of inhibitory mechanism of resveratrol on the hIAPP1-37 oligomer, and the identification of its binding sites on this protein are helpful for the future design and discovery of new amyloid inhibitors.