Objectives: Polyphenols are a structurally diverse class of secondary metabolites found in plants and plant-based foods that have been associated with cardiometabolic-protective effects despite their poor bioavailability. Dairy proteins (e.g., caseins, whey) have been shown to increase polyphenol bioavailability due via protein-polyphenol interactions. Previous research has shown that proteins from pea and hemp have a greater affinity to interact with blueberry polyphenol in vitro compared to whey, suggesting that these proteins may enhance polyphenol bioaccessibility to a greater extent. The objective of this study was to evaluate the impact of protein source and structure on polyphenol bioaccessibility upon the formation of protein-polyphenol complexes in vitro. Methods: Protein from whey, pea and hemp were combined with blueberry polyphenols at a rate of 1 mg protein to 33 ug polyphenols, representative of the nutrient profile of a protein drink containing 1 serving of protein and 1 c blueberries, then underwent in vitro digestion and were lyophilized. Bioaccessibility was evaluated by adding the lyophilized digesta to the apical chamber of a Caco-2 transwell model of the small intestinal barrier. Media was collected from the basolateral chamber after 4 h. Concentrations of blueberry-associated anthocyanins (ACN) and metabolites were quantified in basolateral media using UPLC-QQQ-MS. Results: Analysis of parent ACN in basolateral media revealed that complexation with hemp protein enhanced bioaccessibility of peonidin-aldopentose-hexoside and petunidin-3-glucoside in comparison to other treatments (p < 0.05). Hemp protein complexation also increased enterolatone sulfate, which is associated with cardiometabolic-protective effects. Whey protein enhanced isourolitin A, while pea protein preserved absorption of isovanillic acid 3-O-sulfate (p < 0.05). PERMANOVA revealed differences in ACN and metabolic profiles resulting from each treatment. Conclusions: Complexation of blueberry polyphenols with protein preserves or enhances the bioaccessibility of these compounds, also influencing their metabolism by intestinal epithelial cells. Ongoing studies include a clinical trial to investigate the influence of protein complexation on polyphenol bioavailability and functionality in vivo. Funding Sources: USDA NIFA, Hatch Project COL00413.