Periodontal diseases are biofilm related inflammatory diseases of the supporting tissue of the teeth associated with specific bacteria including Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans and Treponema denticola. Biofilm related diseases can be persistent and hard to resolve due to their increased resistance to antimicrobial agents and host immune responses. The anthelmintic drug Oxantel has previously been shown to inhibit fumarate reductase activity in some pathogenic anaerobic bacteria and inhibit P. gingivalis homotypic biofilm formation. In this study we demonstrate that Oxantel directly inhibited P. gingivalis fumarate reductase activity with a 50% inhibitory concentration (IC50) of 2.2 µM and the planktonic growth of T. forsythia with an MIC of 295 µM, but had no effect on T. denticola growth. Oxantel inhibited P. gingivalis, T. forsythia and T. denticola polymicrobial biofilm formation in a concentration dependent manner with all three species inhibited to a similar degree, demonstrating a synergistic biofilm formation relationship between these three species. Oxantel treatment altered the expression of 28 gene products regulated by the P. gingivalis Fur orthologue Har. In a murine periodontitis model, Oxantel reduced alveolar bone loss to the same level as the uninfected control. These data indicate that Oxantel may have efficacy in the treatment of periodontal diseases in humans.