The immune system’s primary response to injury, stress, or infection is inflammation. It affects many people as they get older and is a response related to diseases such as cancer, osteoporosis, inflammatory bowel disease, cardiovascular disease, obesity, rheumatoid arthritis, and asthma. Therefore, it is important to have effective treatments. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used but they have many side effects and high costs. Natural products have emerged as potential regulators of immune responses and inflammation. Cinnamaldehyde (CM), a plant-derived compound with a simple chemical structure but possessing diverse pharmacological activities, has garnered considerable interest. In this study, we have computationally assessed the CM anti-inflammatory potential and compared it with commercially used anti-inflammatory drugs, namely indomethacin (INDO), diclofenac (DIC), and naproxen (NAP) utilizing various tools. CHEM3D facilitated overlay and alignment analyses, with molinspiration assessed drug likeliness and bioactivity, while vNNADMET, SWISS ADME, and admetSAR were instrumental in studying pharmacokinetics parameters and toxicity, Galaxxrefine was employed for simulation studies, and iGEMDOCK, along with DS-visualizer, aided in the examination of molecular interactions. Additionally, in vitro analysis of serum protein protection and anti-cathepsin B activity was observed at [Formula: see text][Formula: see text]M and [Formula: see text][Formula: see text]M, respectively. The combined findings from in silico and in vitro studies strongly suggest the significant anti-inflammatory potential of CM when compared to commercially available anti-inflammatory drugs.