Ovomucoid (OVM) is an important egg protein that can cause allergic reactions. The allergenicity of the ovomucoid can be reduced by altering its structure. In the study, the excess proteins were salted out using microwave (power 140 W, extraction time 20 s) in combination with ammonium sulfate. The polyacrylamide gel electrophoresis showed that the purity of obtained OVM reached 95%, and the extraction rate was 72%. Subsequently, ultrasound was used for glycation with different substrates. Typically, ultrasound expanded the conformation of OVM to promote glycation by increasing reaction sites. UV absorption spectrum and circular dichroism chromatography have demonstrated the changes in the secondary structure of OVM. At last, ELISA experiments showed that the binding ability of immunoglobulin G was reduced to a varying degree (46.8%−67.1%). In summary, ultrasoundassisted glycation may effectively change the structure of proteins, which could play a potential role in reducing the allergenicity of food.