Periodontitis is a multifactorial chronic inflammatory infectious disease associated with systemic diseases. Proanthocyanidin B2 (PB2), a polyphenol, has been investigated to exhibit antioxidant, anti-inflammatory and anti-cancer pharmacological properties. PB2 has shown good efficacy in treating hepatocellular carcinoma, type 2 diabetes mellitus, and ulcerative colitis. There are few studies on PB2 in treating periodontitis, and the molecular mechanism is unknown. This research focused on the effects of PB2 in Porphyromonas gingivalis-derived lipopolysaccharide (