Periodontitis is a chronic disease that affects the gums and destroys connective tissue. Acanthoic acid (AA), a diterpene in Acanthopanax koreanum, has been reported to have anti-inflammatory activities. The aim of this study was to investigate the anti-inflammatory effects of AA on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs). HGFs were treated with Porphyromonas gingivalis LPS in the presence or absence of AA. The production of inflammatory cytokines IL-8 and IL-6 were measured by ELISA. The expression of NF-κB and TLR4 were detected by Western blotting. The results showed that AA inhibited LPS-induced IL-8 and IL-6 production in a dose-dependent manner. In addition, AA inhibited LPS-induced TLR4 expression and NF-κB activation. In conclusion, AA inhibits LPS-induced inflammatory response in HGFs through inhibition TLR4-mediated NF-κB signaling pathway.