Asthma is one of the most common chronic inflammatory airway diseases worldwide. Although current treatments can control symptoms, they are unable to fundamentally regulate the underlying immunopathological processes. Xiao'er Jiangqi Pingxiao Mixture (JPM) is a clinically used empirical prescription for the treatment of asthma. Previous studies have confirmed its efficacy in improving asthma symptoms, but its underlying mechanism remains to be elucidated. In this study, transcriptomic data from nasal brush samples of pediatric asthma patients (GSE152004) and lung tissue transcriptomic data from asthmatic mice (GSE41665) were integrated. Core targets were identified using machine learning, and their association with the immune microenvironment of asthma was explored through immune cell infiltration analysis. Pharmacodynamic evaluation and mechanistic validation were then performed in an ovalbumin (OVA) -induced asthma mouse model. The pharmacodynamic results showed that JPM significantly reduced the levels of interleukin (IL) -4 and IL-5 in bronchoalveolar lavage fluid (BALF) of model mice and alleviated airway inflammatory infiltration, mucus secretion, and collagen deposition. Machine learning identified seven core genes, among which IL-13 and interleukin-1 receptor-like 1 (IL-1RL1) were significantly positively correlated and closely associated with the infiltration of pro-inflammatory immune cells such as activated dendritic cells and type 1 macrophage (M1).Enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), and real-time quantitative PCR (RTqPCR) further demonstrated that JPM significantly downregulated the protein expressions of IL-13 and IL-1RL1 in BALF, suppressed the positive expressions of complement C1q subcomponent subunit A (C1QA) and subunit C (C1QC) in lung tissues, and reduced the messenger RNA (mRNA) levels of IL-33, thymic stromal lymphopoietin (TSLP), and the complement receptor low-density lipoprotein receptor-related protein 1 (LRP1). Collectively, these findings suggest that JPM may ameliorate the experimental asthma phenotype by interfering with the "epithelial alarmin-complement-mediated presentation-type 2 immune amplification" cascade axis (specifically through inhibiting IL-33/TSLP release, blocking C1QA/C1QC-LRP1 mediated antigen presentation, and modulating the IL-1RL1/IL-13 axis), thereby systematically restoring the helper T cell 2 (Th2) immune microenvironment homeostasis. This study provides an experimental basis for further mechanistic investigation and clinical application of JPM. All animal experiments were approved by the Animal Ethics Committee of China Academy of Chinese Medical Sciences (approval No.: 2026B039).