Objective · To investigate the effects of psoralen and angelicin on inflammation cytokine expression of human periodontal ligament cells (hPDLCs). Methods · hPDLCs were primarily cultured using tissue explant method. Effects of psoralen and angelicin on the cell viability were tested by CCK-8 assay. hPDLCs were stimulated by Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) after treatment with different concentrations of psoralen and angelicin for 2 h. mRNA expression of IL-1β and IL-8 were determined by real-time PCR. Enzyme-linked immunosorbent assay (ELISA) was used to measure the secretion of IL-1β and IL-8. Results · hPDLCs were cultured successfully by tissue explant method. Psoralen and angelicin (≤ 12.5 μg/mL) did not show significant effects on the cell viability of hPDLCs. Pg-LPS markedly elevated the mRNA expression of IL-1β and IL-8,which could be attenuated by psoralen and angelicin in a dose-dependent manner. Likewise, the up-regulated protein secretion of IL-1β and IL-8 could be significantly blocked by psoralen and angelicin. Conclusion · Psoralen and angelicin could attenuate the inflammatory response of hPDLCs induced by Pg-LPS. Therefore, psoralen and angelicin may act as natural agents to prevent and treat periodontitis.