N-acyl hydrazides are highly intriguing to medicinal chemists due to their extensive range of biological actions. Many nonsteroidal anti-inflammatory drugs (NSAIDs) available on the market are limited, and the potential risks related to the inflammation process provide an immense challenge for medicinal chemists to discover more effective anti-inflammatory drugs.In the present work, a variety of N-acyl hydrazide derivatives were prepared by a dual-step reaction. Cyanoacetohydrazide, 2-hydroxy-1-naphthaldehyde, Ethanol, pyridine, substituted benzaldehydes, Glacial acetic acid are used for the synthesis. Characterization was performed by UV, IR, and NMR spectral techniques. Then the potential of these compounds against the COX-2 receptor for anti-inflammatory activity was analyzed using the insilico method.Carrageenan-induced Paw Edema method was used for in vivoantiinflammatory activity. The antioxidant activity of the compounds was evaluated by DPPH and nitric oxide assays. The compound 4e exhibited anequivalent but marginally superior docking score than the standard celecoxib whereas compounds 4d, 4f and 4g displayed comparable docking scores. Molinspiration studies revealed that there are no Lipinski violations in all the synthesized compounds.The trimethoxy derivative (4d) hasanti-inflammatory activity similar to celecoxib, while the dimethoxy (4e), 2-hydroxy-3-methoxy (4g), and 4-hydroxy (4f) derivatives showed good anti-inflammatory activity. Among all the compounds, 4g showed good antioxidant activity in both assays, with 71% and 56% inhibition.