Protocatechuic acid (PCA), a major metabolite of anthocyanins, has been shown to have antioxidant, antitumoral, and anti-inflammatory activities. In this study, we investigated the anti-inflammatory effects of PCA on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs). The effects of PCA on LPS-induced inflammatory cytokines IL-6 and chemokines IL-8 in HGFs were detected by ELISA. The expression of NF-κB and PPAR-γ was detected by Western blot analysis. Our results demonstrated that PCA suppressed IL-6 and IL-8 production in LPS-stimulated HGFs. We also found that PCA inhibited LPS-induced NF-κB activation. Furthermore, the inhibition of PCA on LPS-induced IL-6 and IL-8 production can be reversed by PPAR-γ antagonist GW9662. In conclusion, the anti-inflammatory mechanism of PCA is associated with activating PPAR-γ, thereby inhibiting LPS-induced inflammatory response.