Inflammation is the body's signal indicating injury, which manifests as pain and swelling. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as mefenamic acid, are used to reduce such pain and swelling. However, side effects like gastric pain have led people to turn to herbal-based treatments. Soursop leaves (Annona muricata) are one such plant commonly used. These leaves contain active compounds such as flavonoids, which have potential anti-inflammatory properties. An in silico approach was employed to predict the anti-inflammatory potential of these compounds. Selected compounds from soursop leaves were docked against inflammatory target proteins, namely COX-1 (PDB: 3KK6) and COX-2 (PDB: 5IKR). Additionally, Lipinski's Rule of Five (Ro5) was predicted for the compounds using available online tools. The in silico results showed that 2-Hexadecen-1-ol, 3,7,11,15-tetramethyl shared 83.33% amino acid residue similarity with COX-1 and a binding affinity of -7.4 kcal/mol using celecoxib as a positive control, while it exhibited 53.33% amino acid residue similarity with COX-2 and a binding affinity of -6.6 kcal/mol using mefenamic acid as a positive control. These findings suggest that 2-Hexadecen-1-ol, 3,7,11,15-tetramethyl has potential as both a COX-1 and COX-2 inhibitor. However, its Log P value exceeded the recommended limit (Log P < 5), which may hinder oral absorption. Therefore, 2-Hexadecen-1-ol, 3,7,11,15-tetramethyl shows potential as a COX-1/COX-2 inhibitor but may face challenges in oral absorption.