Asthma is a kind of chronic inflammatory and allergic disease. Peptides have showed significant potential for asthma therapeutics. Our study aims to identify the differential peptidomic profiles between asthmatic and non-asthmatic mice. Methods and results: House dust mite (HDM) was utilized to build an asthmatic mouse model. Lung tissues were tested by histological analysis and liquid chromatography-mass spectrometry (LC-MS/MS). Histological analysis of lung tissues showed eosinophils infiltration, thickening of the bronchial wall, swelling, and hyperemia of the mucosa. In which, 108 of 1564 peptides were identified and showed significant differential expression (fold change >2 or fold change <0.5, P-value <0.05), containing 44 upregulated and 64 downregulated peptides. GO analysis demonstrated that the functional precursor proteins of the identified peptides were primarily associated with actin polymerization or depolymerization, receptor-mediated endocytosis (RME), and regulation of the inflammatory response. KEGG analysis revealed thatthe peptides were associated with soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) interactions in vesicular transport, bacterial invasion of epithelial cells, and tight junction signaling pathways. Precursor proteins analysis revealed that peptides derived from glutamic acid-rich protein-like 3 (SH3BGRL3) might be related to the incidence of asthma. Conclusions: Our results provide evidence for the candidate treatment sites of peptides in asthma.