Abstract: To investigate the effects of in vitro digestion on the phenolic compounds and bioactivity of walnut pellicle polyphenols extracts, the walnut pellicle polyphenols extracts were subjected sequentially to simulated oral, gastric and small intestinal digestion in this study. The total phenolic content of the walnut pellicle polyphenols extracts was measured at different stages of digestion. Antioxidant and hypoglycemic activities of the walnut pellicle polyphenols extracts were evaluated using DPPH radical scavenging rates, ABTS⁺ radical scavenging rates, and α-glucosidase and α-amylase inhibition rates. The results showed that digestion led to a significant decrease (P<0.05) in the total phenolic content and bioaccessibility, and the total phenolic content decreased from 695.27 mg GAE/g to 437.58 mg GAE/g, with the most significant degradation in the small intestine stage. A total of 224 phenolics were identified in the walnut pellicle polyphenols, and the main polyphenols were gallic acid, corilagin, 1-O-galloyl-D-glucose, and chlorogenic acid. During digestion, the antioxidant capacity of walnut pellicle polyphenols decreased (P<0.05), with DPPH· radical scavenging rate dropping from 90.18% to 35.73% and ABTS⁺ radical scavenging rate declining from 90.84% to 47.33%. Simultaneously, their hypoglycemic activity also weakened (P<0.05), manifested by a 36.1% decrease in α-glucosidase inhibition rate and a 72.44% decrease in α-amylase inhibition rate. At the end of digestion, the walnut pellicle polyphenols were degraded or transformed, but they still exerted some biological activities. During the digestion process, the changes of DPPH∙ and ABTS⁺∙ scavenging rates, α-glucosidase and α-amylase inhibition rates were positively correlated with the changes of total phenol content. This study demonstrated that walnut pellicle polyphenols have the potential to develop functional foods, and also provided a theoretical basis for the resource utilization of walnut processing by-products.