Objective: To evaluate the effect of a pomegranate-containing mouthrinse on plaque, determine whether it has any adverse effects, and evaluate its antibacterial properties against selected periodontopathogens in vitro. Method and Materials: Thirty periodontally healthy volunteers, randomly divided into three groups, refrained from all mechanical oral hygiene measures for 4 days and used one of the randomly assigned mouthrinses (A, pomegranate; B, chlorhexidine; or C, distilled water [placebo]) twice daily. The Plaque Index (PI) was assessed at days 0 and 5. Adverse effects were also evaluated. Pomegranate extract was tested against Aggregatibacter actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.), and Prevotella intermedia (P.i.). Results: In all groups, the PI significantly increased from the baseline to day 5 (P .1). The pomegranate mouthrinse created no adverse effects. There was a statistically significant difference (P .05) between the chlorhexidine and placebo rinse and the pomegranate and placebo rinse, but no statistically significant difference was found between the chlorhexidine and pomegranate rinse with respect to the PI. Pomegranate extract showed inhibition of all three strains of periodontopathogens at various concentrations. Conclusion: These results indicate that the pomegranate mouthrinse has an antiplaque effect. Pomegranate extract is efficacious against A.a., P.g., and P.i. strains in vitro. Pomegranate mouthrinse should be explored as a long-term antiplaque rinse with prophylactic benefits. Keywords: Aggregatibacter actinomycetemcomitans (A.a.), antiplaque agent, mouthrinse, pomegranate, Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.)