Periodontitis is caused by periodontopathic bacteria such as Porphyromonas gingivalis and Tannerella forsythia. P. gingivalis has several biologic activities such as protease secretion. Inhibition of protease activities of periodontopathogens is one of the most effective strategies to prevent the progression of periodontitis. Lactoferrin, an iron-binding glycoprotein, is considered to be a useful tool for this purpose, and lactoferrin supplements may be effective for health promotion. In this study, the effect of purified lactoferrin on P. gingivalis and T. forsythia protease was examined. The effect of lactoferrin supplement on protease activity was also tested. The purified lactoferrin inhibited the protease activity of both periodontopathogens. Lactoferrin supplement also exhibited the inhibitory effect. From these results, lactoferrin and lactoferrin supplements is considered to contribute to the prevention of periodontitis by inhibiting the protease activity of periodontopathogens.