Background: This study investigated on antioxidant activity of Piper caninum and cyclooxygenase-2 inhibition by methoxylated flavones. Materials and methods:The present study was carried out to quantify the total phenolic content and free radical scavenging activities of the crude extracts by Folin-Ciocalteu and 1,1-diphenyl-2-picrylhydrazyl free radical scavenging assay respectively. Results: Methanolic extracts of Piper caninum exhibited the highest total phenolic content and free radical scavenging activities. All the pure compounds possessed significant cyclooxygenase-2 inhibition at physiological concentrations. Conclusion: Based on in vitro and molecular docking, we therefore suggest that Piper caninum methoxylated flavones are potent inhibitors of cyclooxygenase-2 at physiological concentrations