Precise prediction of the fraction of compounds reaching the portal vein (FaFg) in humans, which could indicate the rate-limiting step of polyphenol metabolism, is particularly important for accurately evaluating the efficacy and safety of polyphenols. In this study, we aimed to develop a novel in vitro method to predict human FaFg of polyphenols using commercially available human induced pluripotent stem cell-derived small intestinal epithelial cells (hiPSC-SIECs). First, the chemicals were used at fixed test concentrations, considering their physicochemical properties and cytotoxicity. The apparent permeability coefficient (P