Galley Proof Current treatments for Chronic Obstructive Pulmonary Disease (COPD) focus on alleviating symptoms, slowing disease progression, and enhancing patients' quality of life. However, existing COPD medications are associated with significant side effects, particularly during long-term use. Natural compounds are increasingly explored as alternative therapies for COPD due to their potential for reduced adverse effects. Laminaria japonica, a brown seaweed species, has attracted attention for its bioactive compounds and health-promoting properties. This study aims to identify key target proteins in COPD and evaluate bioactive compounds from Laminaria japonica as alternative therapeutic agents through differentially expressed gene (DEG) analysis and molecular docking. Critical COPD-associated genes were identified by analyzing DEGs to map gene-pathway relationships and assessing Laminaria japonica compounds computationally. The F2 (coagulation factor II) and BDKRB1 (bradykinin receptor B1) genes exhibited significant upregulation (log2 fold change >1), highlighting them as potential therapeutic targets. Pathway enrichment analysis revealed that complement and coagulation cascades, platelet activation, and inflammatory pathways play central roles in COPD pathogenesis. Among 47 compounds screened for interactions with F2 (PDB ID: 1A2C) and BDKRB1 (PDB ID: 7EIB), docosatrienoic acid demonstrated the strongest binding affinity (MolDock score:-15598; Rerank score:-11868 for F2; MolDock score:-14639; Rerank score:-11296 for BDKRB1). These findings suggest that docosatrienoic acid, a compound derived from Laminaria japonica, holds promise as an inhibitor of F2 and BDKRB1, offering potential therapeutic benefits for COPD. © 2025 Pratomo et al.