Purpose <p>Asthma is a chronic inflammatory airway disease characterized by complex genetic and immunological interactions. Emerging evidence highlights the role of the gut–lung axis, wherein gut microbial metabolites modulate systemic and airway inflammation. This study aimed to elucidate the therapeutic potential of gut microbial metabolites as anti-asthmatic agents through a network pharmacology-based analysis.</p> Methods <p>Seventeen gut microbial metabolites with reported immunoregulatory properties were selected from literature. Their molecular targets were predicted using SwissTargetPrediction and SuperPRED, while asthma-associated genes were retrieved from GeneCards, OMIM, CTD, and TTD databases. Overlapping genes between metabolites and disease targets were identified, and a protein–protein interaction (PPI) network was constructed and analyzed to determine hub genes. Functional enrichment analysis was performed to identify significantly enriched Gene Ontology (GO) terms and KEGG pathways.</p> Results <p>A total of 6,034 asthma-related genes and 23 hub genes were identified, of which 12 overlapped with metabolite-predicted targets. GO enrichment revealed biological processes such as positive regulation of protein transport, telomerase activity, carbohydrate metabolism, and myeloid cell differentiation. Enriched cellular components included the plasma membrane, Wnt signalosome, and transcription regulator complex, while molecular functions involved nuclear receptor and β-catenin binding. KEGG analysis indicated significant enrichment in Wnt, PI3K–Akt, MAPK, TGF-β, and cytokine–cytokine receptor interaction pathways.</p> Conclusions <p>Gut microbial metabolites may be associated with pathways involved in airway inflammation and remodeling. These findings reveal novel molecular targets and provide a mechanistic basis for developing microbiome-derived adjunct therapies for asthma.</p> Graphical Abstract <p></p>