Background: Asthma is characterized by chronic airway inflammation and oxidative stress. Ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation, has emerged as a key pathological mechanism in asthmatic airway injury. Soufeng Yuchuan (SFYC) decoction, a classic Chinese herbal formula, has long been used clinically for asthma, yet its precise mechanism remains unclear. Purpose: This study aimed to elucidate the therapeutic mechanism of SFYC in asthma, with a focus on its regulatory effect on ferroptosis using integrated multi-omics and experimental validation. Methods: OVA-induced asthmatic rat models and erastin-induced ferroptosis models in BEAS-2B cells were established. Proteomics and metabolomics were performed on lung tissue and serum. Key ferroptosis-related targets (GPX4, SLC7A11/SLC3A2, GCLC, GSS, VDAC2) were validated by Western blotting, RT-qPCR, and biochemical assays. The direct anti-ferroptosis effect of SFYC-containing serum was compared with ferrostatin-1 and blank serum in vitro. Results: Integrated omics revealed that ferroptosis, glutathione metabolism, and ROS pathways were the core targets of SFYC. In vivo, SFYC significantly reduced airway inflammation, ROS accumulation, restored pulmonary GSH content, upregulated GPX4/GCLC/GSS/SLC7A11/SLC3A2, and downregulated VDAC2 (P < 0.05). In vitro, SFYC-containing serum effectively reversed erastin-induced lipid peroxidation, iron overload, GSH depletion, ROS elevation, and apoptosis in BEAS-2B cells with efficacy comparable or superior to ferrostatin-1. Conclusion: SFYC ameliorates asthmatic airway inflammation primarily through targeted inhibition of ferroptosis, providing the first evidence that this traditional formula exerts anti-asthmatic effects via the ferroptosis pathway and offering a novel mechanistic basis for its clinical application.