The degradation of acidic gastric juice on immunoglobulin Y (IgY) leads to destruction on the structural and loss of the bioactivity, limiting the bioavailability of oral IgY and its research or application in adjuvant treatment of diseases. In this work, it was surmounted with IgY‐loaded chitosan–liposomes prepared by supercritical carbon dioxide‐assisted method. A range of chitosan concentrations (0%, 0.5%, 0.8%, 1.1%, and 1.4%) were selected to explore the influence of chitosan concentration on the encapsulation effectiveness, stability, and in vitro‐simulated digestive release properties of liposome‐encapsulated IgY. The results displayed that owing to the robust interaction between chitosan and liposomes, the particle size, encapsulation efficiency, and stability of liposomes reached the optimal state at a chitosan concentration of 0.8%, with the encapsulation efficiency reaching 77.51%. Moreover, the liposomes could be stored at 4°C for 9 days without obvious sedimentation. The zeta potential of liposomes containing 0.8% chitosan was higher than that of samples without chitosan at high salt concentration treatment. In vitro release experiments demonstrated that liposomes fitted well in the Peppas equation. Chitosan‐coated liposomes were capable of delaying the release of IgY in the stomach during simulated digestion, allowing more IgY to be released in the intestine. To sum up, Chitosan played a vital role in maintaining the stability and encapsulation of IgY, and the results of this work provide a theoretical basis for the development and utilization of chitosan and the protection of activity of IgY when administered orally.

IgY serves as a bioactive substance with anti‐inflammatory, antibacterial, and antioxidant functions. However, it is far from satisfactory for the oral delivery activity of IgY. Encapsulation of liposomes contributed to alleviate the release of IgY in the stomach. However, liposomes were less stable and not efficient enough to encapsulate IgY. This study demonstrated that the addition of 0.8% chitosan could effectively enhance the encapsulation efficiency of liposomes and improved the stability of liposomes. It might contribute to the solution of the oral delivery activity of IgY and provide a promising idea for the utilization of chitosan.