Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain, inflammation, and fever due to their effectiveness and accessibility. These drugs exert their therapeutic action primarily by inhibiting cyclooxygenase (COX) enzymes, thereby reducing the synthesis of prostaglandins, which are key mediators of inflammation and pain.In order to assess the binding affinity and interaction patterns of a few NSAIDs—ibuprofen, aspirin, sulindac, and indomethacin against the Cyclooxygenase-1 (COX-1) enzyme (PDB ID: 6Y3C), the current study focuses on molecular docking studies. According to the docking data, all of the chosen drugs have good binding interactions; ibuprofen has the highest binding affinity, followed by aspirin, sulindac, and indomethacin. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) study was carried out in addition to docking studies to evaluate the pharmacokinetic and safety profiles of these medications. The findings imply that the chosen NSAIDs have adequate metabolic stability and excretion profiles along with good absorption and distribution characteristics. However, some restrictions were noted, including the possibility of hepatotoxicity and gastrointestinal distress. Overall, this work highlights the need for safer substitutes with fewer side effects while supporting the continued use of NSAIDs and highlighting the need of combining molecular docking with ADMET analysis in understanding drug behavior.