Allergen immunotherapy (AIT) has developed over the last few decades and has emerged as a promising treatment. House dust mite (HDM) is a target allergen in AIT, and various modified HDM allergens have been improved for their efficacy. Moreover, clinical trials have proved their significantly therapeutic effects in allergy. This article review focuses on HDM allergens developed for AIT efficacy, and determines that their action mechanisms are strongly based on immune tolerance. Treatments for HDM allergens have been optimized by modification or/and addition of adjuvants, and clinically evaluated by subcutaneous and sublingual administration. Representative allergens used in AIT are chemically modified allergoids and recombinant allergens, including altered epitopes. The effective mechanisms subsequent to AIT include the suppressive actions of interleukin-10 and transforming growth factor-β secreted by regulatory cells, including regulatory T cells and regulatory B cells, and isotype switching from immunoglobulin E to immunoglobulin G4. Further studies of AIT are needed to achieve the milestone in treating allergies.