Background: Bioactive compounds need to resist food processing, be released from the food matrix, and be bioaccessible in the gastrointestinal tract in order to provide health benefits. Bioactive compounds isolated from peach pomace (PP) were encapsulated using four different wall materials to improve their stability and to evaluate the effects of in vitro gastrointestinal digestion, as well as chemometric modeling among obtained encapsulates. Methods: Phenolics and carotenoids content, antioxidant, antihyperglycemic, anti-inflammatory, and cell growth activities were evaluated after gastric and intestinal digestion steps. Chemometrics classification analysis–principal component analysis and hierarchical cluster analysis revealed grouping among encapsulates. Results: The encapsulation of PP bioactive compounds showed a protective effect against pH changes and enzymatic activities along digestion, and thereby contributed to an increase in their bioaccessibility in gastric and intestinal fluids. Conclusions: The obtained results suggest protein and polysaccharide carriers and the freeze-drying technique, as an efficient method for the encapsulation of bioactives from PP, could find use in the food and pharmaceutical industry.