Red grape pomace, a by-product generated during red wine manufactureingand rich in phenolic compounds, particularly anthocyanins, can be used to obtain natural food additives with antioxidant properties, thus improving their functional characteristics. As polyphenols, and anthocyanins specifically, tend to oxidize, which results in a loss of bioactivity, the microencapsulation of these compounds is proposed to prolong their stability during processing and storage. From a mixture of red grape pomace obtained as residues from Vitis vinifera L. wine production, microencapsules (maltodextrin, whey proteins, and chitosan) rich in pomace polyphenols were developed by means of spray drying. These microcapsules were then added to yogurt (skim, natural, and sweetened with Stevia), a dairy matrix for mass consumption, with low cost and variable storage periods. The resulting yogurts (YM) were subjected to in vitro gastrointestinal and colonic digestion. Then, polyphenol extracts were obtained from the different stages of digestion. These extracts were purified using SPE columns, and their polyphenol content was evaluated via FOLIN CT. The impact of these processes on bioactivity was assessed by analyzing the effect on antioxidant and antiproliferative responses in vitro in human intestinal cells via flow cytometry. The results obtained contribute to our understanding of how the modifications that occurred during the digestion process impact the final biological response achieved.