Liposomes containing theobromine, caffeine, catechin, epicatechin, and a cocoa extract were fabricated using microfluidization and sonication. A high encapsulation efficiency and good physicochemical stability were obtained by sonication (75% amplitude, 7 min). Liposomes produced at pH 5.0 had mean particle diameter ranging from 73.9 to 84.3 nm. The structural and physicochemical properties of the liposomes were characterized by transmission electron microscopy, confocal fluorescence microscopy, and antioxidant activity assays. The release profile was measured by ultra-high performance liquid chromatography coupled to diode array detection. The bioaccessibility of the bioactive compounds encapsulated in liposomes was determined after exposure to a simulated in vitro digestion model. Higher bioaccessibilities were measured for all catechins-loaded liposome formulations as compared to nonencapsulated counterparts. These results demonstrated that liposomes are capable of increasing the bioaccessibility of flavan-3-ols, which may be important for the development of nutraceutical-enriched functional foods.