Abstract: Food allergy has become a growing food safety concern at a global scale. Potential allergenicity assessment of food allergens will help to better understand the characteristics of food allergens and their effects on the immune system of allergic people. Simulated digestion experiment has become a powerful means for assessing the potential allergenicity of food allergens. The digestive stability of food allergen protein provides an important reference basis for its allergenicity assessment results. However, not all food allergens have strong digestive stability. The potential allergenicity of food allergen depends on the digestive stability of the allergen protein when passing through the gastrointestinal tract, and on the other hand the abundance of allergen epitopes with immunostimulatory capabilities in the digestion products. The application of different simulated digestion methods has an important impact on the authenticity and comparability of the assessment results of the potential allergenicity of food allergens. This article systematically describes the advantages and disadvantages of in vivo and in vitro simulated digestion methods and their recent application progress in the potential allergenicity assessment of food allergens, and reviews the relationship between the digestive stability and potential allergenicity of food allergens. This paper would contribute to the further improvement and development of the potential allergenicity assessment system of food allergen.