Sesame is one of the new “big eight” priority allergic foods. Sesame allergic reaction has attracted more and more attention all over the world because of its potential severity and increasing prevalence. Therefore, the study of sesame allergenicity mitigation technology is of great importance in ensuring food safety. The structures and immunological properties of the main sesame allergen (Ses i 1-Ses i 7), and the principles and research progress of the allergenicity mitigation technologies were summarized. The reported seven sesame allergens belonged to 2S albumin, 7S vicilin-type globulin, oleosin, and 11S globulin, among which 11S globulins and 2S albumins are the major allergen protein. Thermal processing techniques were used to mitigate the allergenicity of sesame, mainly through boiling, microwave, baking and so on to cause the depolymerization and denaturation of allergens, and then destroy the allergenic epitopes. Non-thermal processing techniques such as high pressure, irradiation, fermentation, enzymolysis and so on, could influence protein structure through the changes of chemical bonds such as hydrogen bonds and hydrophobic bonds, and the breakage of polypeptide chains, so as to cover or degrade directly the allergenic epitopes. At the same time, referring to other food allergen, the potential mitigation technologies of sesame allergens were further proposed, including pulsed electric field, cold plasma, ultrasonic wave, pulsed light, glycosylation modification and compound processing technology. In the future, it is necessary to study the epitopes of different sesame allergens, the effects of different processing technologies on the allergens structure and allergenicity, and carry out the allergenicity evaluation through serology, cell and animal models, and etc., so as to clarify the main mechanism of sesame allergenicity mitigation, and offer a theoretical basis and scientific guidance for the production of hypoallergenic or desensitized sesame products.