Background House dust mite (HDM) is a well‐known cause of asthma. Allergen‐specific immunotherapy (AIT) can only modify the natural course of the disease. Conventional routes of HDM AIT are subcutaneous or sublingual. Subcutaneous immunotherapy (SCIT) has a disadvantage of systemic hypersensitive reaction, and the sublingual immunotherapy has a disadvantage of local allergic reaction and low drug adherence. Objective To overcome the weak points of conventional AIT, we developed a HDM loaded biodegradable microneedle patch (MNP) for transdermal immunotherapy (TDIT). We aim to demonstrate the efficacy of TDIT in murine asthma model triggered by HDM compared with conventional SCIT. Methods To make HDM asthma mouse model, 5‐week‐old BALB/c female mice were sensitized and challenged by intranasal administration of HDM. The mice were divided into 5 groups: sham, asthma, low (10 µg) and high dose (100 µg) SCIT, and TDIT (10 µg). To make HDM loaded MNP, droplet‐born air blowing method was used. Airway hyperresponsiveness and allergic inflammation markers were analysed by bronchoalveolar lavage fluid, immunohistochemistry, serum immunoglobulin (Ig) analysis, and lung cytokine assays. Results Airway hyperresponsiveness was ameliorated by TDIT. Eosinophilic inflammation in bronchoalveolar lavage was improved without adverse reactions. Reduction of Th2 (IL‐4, IL‐5, and IL‐13) cytokines, and HDM‐specific IgE, induction of Treg (IL‐10, TGF‐β), Th1 (IFN‐γ) cytokines were observed. Eosinophilic infiltration, goblet cell hyperplasia, and subepithelial fibrosis were also alleviated by TDIT. These changes were more significant in the TDIT group than in subcutaneous AIT group. Conclusion In conclusion, HDM loaded biodegradable TDIT is a novel treatment option to treat asthma which showed more effectiveness and may have better safety profiles than conventional SCIT.