Abstract: Objective:To study the inhibitory effect of berberine (BBR) on Porphyromonas gingivali (Pg) and explore its mechanism. Methods:The minimum inhibitory concentration (MIC) of BBR on the inhibition of standard strains Pg ATCC33277 and hypervirulent strains Pg W83 was detected by concentration gradient dilution method. The minimum bactericidal concentration (MBC) of BBR on Pg ATCC33277 and Pg W83 was detected by blood plate experiment. The effect of BBR on bacterial activity of Pg ATCC33277 was studied by MTT. The effect of BBR on the cell walls of Pg ATCC33277 was determined by alkaline phosphatase activity. The effect of BBR on the morphology of Pg ATCC33277 was observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Results:The MIC and MBC of BBR for Pg ATCC33277 and Pg W83 were 15.625 μg/mL. At this concentration, BBR can significantly reduce the bacterial activity of Pg ATCC33277 (P<0.05), reduce the activity of alkaline phosphatase after 12 hours (P<0.05). Pg ATCC33277 cells were deformed and wrinkled after BBR action and lost the normal bacterial morphology under SEM and TEM. Conclusions:BBR has a significant inhibitory effect on Pg ATCC33277 and Pg W83. It may reduce bacterial viability by disrupting cell walls and cell membranes.