Objectives Houttuynia cordata Thunb., a member of the Saururaceae family, has been demonstrated to have potential in the treatment of different diseases. For the first time, aristolactam BII was isolated from the aerial part of Houttuynia cordata Thunb. and the anti-inflammatory effect of the extract and aristolactam BII was evaluated. Methods After using chromatography to separate and obtain the compound, Nuclear Magnetic Resonance was used to identify the compound. An in vivo model of carrageenan-induced paw edema on mice was performed to test the anti-inflammation of the extract and compound. Furthermore, a ligand docking experiment was performed to determine the binding free energy of aristolactam to inflammatory proteins including COX-1, COX-2. Results The findings showed that aristolactam BII effectively reduced the severity of the edema, similar to diclofenac, whereas the methanol extract showed low effectiveness. Particularly, the swelling rate of 50 mg/kg aristolactam BII treated mice was only 26.2 +/- 7.1% (p < 0.01) after 5 h treatment. The in silico results described that aristolactam BII might inhibit COX-1 and COX-2 via creating h-bonds at the sites of Ser 530 residues. Conclusion Our results demonstrate the potential anti-inflammatory activity of aristolactam BII. This study would provide more fundamental knowledge about the bioactivities of aristolactam BII isolated from Houttuynia cordata.