Allergic diseases are immune system dysfunctions mediated by mast cell (MC) activation stimulated by specific allergens. However, current small molecular MC stabilizers for allergic disease prevention often require multiple doses over a long period of time and are associated with serious side effects. Herein, we develop a diselenide-bridged mesoporous silica nanostabilizer, proving that it could specifically target sensitized MCs via the recognition of IgE aptamer and IgE. Meantime, the IgE aptamer can also mitigate allergic reactions by preventing re-exposure of allergens from the surface of sensitized MCs. Furthermore, the diselenide-bridged scaffold can be reduced by the intracellular excessive ROS, subsequently achieving redox homeostasis via ROS depletion. Finally, the precise release of small molecular MC stabilizers along with the biodegradation of nanocarrier can stabilize the membranes of MCs. In vivo assays in passive cutaneous anaphylactic (PCA) and allergic rhinitis (AR) mice indicated that our current strategy further endowed it with a high efficacy, long-term therapeutic time window, as well as negligible inflammatory side effects for allergic diseases, offering a promising therapeutic strategy for the clinical generalization of allergic diseases.