Abstract Background Oral immunotherapy (OIT) is a promising approach for treating IgE‐mediated food allergy, but safety concerns limit its use. Heat‐denaturation of food allergens may reduce allergic reactions by lowering IgE binding. Here, we examined how heat‐induced structural changes in egg allergens affected basophil activation in egg‐allergic patients. Methods Gal d 1 and Gal d 2 were subjected to heat treatment and analyzed for structural changes using SDS‐PAGE, ELISA, NanoDSF, and circular dichroism. Peripheral blood samples were obtained from a cohort of 42 patients with egg allergy. Patients' sensitization status was determined, and basophils were isolated and incubated with native or heat‐denatured egg allergen preparations. Basophil activation was assessed by measuring leukotriene release as a marker of degranulation. Results Heat‐denaturation induced time‐ and temperature‐dependent structural changes in both Gal d 1 and Gal d 2, resulting in reduced IgE binding capacity. In functional assays, heat‐denatured allergens elicited weaker basophil degranulation responses compared to native allergens, but the effect varied depending on individual IgE sensitization profiles. Among patients who reacted to heat‐denatured allergens, egg‐white IgE levels tended to be higher, although requiring higher doses to trigger leukotriene release. Conclusion Heat‐denaturation of egg allergens reduces IgE‐binding and basophil activation, although residual reactivity persists in patients with higher sensitization profiles. Importantly, higher allergen doses were needed to trigger basophil degranulation compared to native allergens, indicating a reduction in allergenic potency. These findings highlight the potential of heat‐denatured egg allergens as safer starting materials for OIT, particularly within personalized, stepwise desensitization protocols, warranting further clinical investigation.