The by-product of extracting oil from sesame has good functional properties for use in the development of new food products. In this study, the effect of simulated gastrointestinal digestion on the bioaccessibility of phenolic compounds, as well as the antioxidant, antidiabetic, and hypoglycemic properties of a beverage from sesame by-products was analyzed. Oral digestion significantly decreased the total phenolic content of the beverage, while the total flavonoid content increased. Both phytochemicals increased after gastric and intestinal digestion. Twenty-five phenolic compounds were characterized in the sesame by-product beverage, including feruloylquinic acid, which was present in all the digestive fractions analyzed. The most abundant free phenolic was quercetin, which was also present in all the digested fractions. On the other hand, the most abundant phenolic in the digested fractions was isorhamnetin. During gastrointestinal digestion, the antioxidant activity and inhibitory effects on the α-glucosidase and DPP-IV of the beverage significantly improved, while the ability to inhibit the α-amylase significantly increased during oral digestion, remaining constant throughout digestion. Correlation analysis indicated that flavonoids, including quercetin, may be the compounds with the greatest effect on the evaluated activities. The results of this study not only improve the understanding of the impact of gastrointestinal digestion on the bioaccessibility of phenolic compounds but also suggest potential applications in formulating functional foods with enhanced antioxidant, hypoglycemic, and antidiabetic properties, contributing to the development of health-promoting food products.
