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Polyphenols are known to interact with protein fractions of feed ingredients in the digestive tract thereby affecting the digestibility. These effects may differ depending on the chemical composition of the protein fractions. Thus, the objective of the study was to study the impact of a tannin-rich chestnut extract (CHE) on the in-vitro digestibility (IVD) of soy protein isolate (SPI), screw-pressed soybean (SPS) and solvent-extracted soybean (SES). In addition, CHE-derived metabolites were tested for their effects on intestinal epithelial integrity. The SPI, SPS, and SES were digested in vitro without (SPI-, SPS-, SES-) or with CHE (SPI+, SPS+, SES+) or as a control (C) solely CHE. The metabolites and the polyphenols content after digestion of the soy-based products with or without CHE were quantified. The trans-epithelial resistance (TEER) was monitored in porcine jejuna in the presence of CHE-derived metabolites at three dilutions (1:4, 1:8, and 1:16 v/v) or in their absence. The claudin-1 (CLDN1), occludin (OCLN) and zonula occludens-1 (ZO1) tight junctions-protein expressions were determined. Finally, the effects of CHE-metabolites against indomethacin (INDO)-induced decrease of TEER were tested ex vivo. The CHE decreased the IVD (P < 0.05) and decreased the detectable polyphenol content (P < 0.05) after digestion of CHE with SPI, SPS, or SES. The SPI and SPI+CHE were the samples with the highest content of metabolites generated after the digestion, while CHE presented the lowest content of metabolites. No detrimental effects on TEER were observed. The 1:8 dilution increased (P < 0.05) both ZO1 and OCLN protein expression by up to + 60% compared to the control, while the dilution 1:16 increased ZO1 expression by + 100% without affecting OCLN expression. The 1:16 dilution also protected the jejunum from the effects induced by INDO. These results suggest that the anti-nutritional effects exerted by CHE on soy-based meals IVD may depend on the meal's chemical composition. Moreover, we showed that CHE polyphenols exert protective effects on the intestinal epithelium integrity ex vivo at low concentrations. • Chestnut extracts inhibit in vitro digestibility and the total polyphenol content in soy-based products depends on their chemical composition. • Chestnut extracts are an important source of polyphenols and digestive processes affect their bioavailability. • Low concentrations of metabolites obtained by the chestnut extracts' digestion exert protective effects at intestinal level. [ABSTRACT FROM AUTHOR]