Flavonoids, found in common vegetables and fruits, have health benefits that are often limited by their low bioavailability. Excipient emulsions provide an effective strategy to overcome these obstacles. However, the nature of the emulsifier used to formulate excipient emulsions and the chemical structure of the flavonoids both affect the bioaccessibility of the flavonoids. The purpose of this study was to investigate the impact of the interfacial properties of excipient emulsions on the in vitro gastrointestinal fate of representative structural flavonoids (quercetin, kaempferol, and apigenin) through the INFOGEST method. Tween 80 (TW80) (a nonionic surfactant) was more effective at reducing the oil-water interfacial tension than whey protein isolate (WPI) (a protein-based emulsifier) or octenyl succinic anhydride (OSA)-modified starch (MS) (a polysaccharide-based emulsifier). Moreover, TW80 created excipient emulsions with smaller oil droplets, which were more resistant to oral and gastric conditions. The WPI-emulsions underwent severe flocculation in the gastric phase, leading to an appreciable increase in particle size (from 220 to 3000 nm). The TW80-coated oil droplets were more digestible than WPI- or MS-coated ones. This was attributed to the larger lipid surface area for lipase attachment. The bioaccessibility of quercetin, kaempferol, and apigenin was also affected by emulsifiers: TW 80 (25% to 45%) > WPI (14% to 29%) ≈ MS (15% to 25%). Flavonoid bioaccessibility appeared to be related to their molecular properties. This study provides guidance for the design of effective excipient emulsions to enhance the bioavailability of flavonoids. © 2024 Society of Chemical Industry.