Periodontitis is a common chronic inflammatory disorder of bacterial origin, which affects the tooth-supporting tissues. A wide range of evidences suggests that Porphyromonas gingivalis plays a key role in the initiation and progression of chronic periodontitis. This Gram-negative anaerobic bacterium produces several types of proteolytic enzymes, including gingipains, collagenases, and a dipeptidyl aminopeptidase IV. Although these enzymes have physiological functions for P. gingivalis, they have been suggested to play multiple roles in the pathogenic process of periodontitis. Indeed, P. gingivalis proteases hydrolyze a variety of serum and tissue proteins thus contributing to neutralize the immune defense system and to cause tissue destruction. Considering the key roles that P. gingivalis proteases may play in the pathogenesis of periodontitis, inhibitors of these enzymes are considered potentially new therapeutics agents. In recent years, several groups have identified natural plant-derived inhibitors effective on P. gingivalis proteases. More specifically, polyphenols isolated from cranberry and green tea were found to inhibit several proteases produced by P. gingivalis. This paper will discuss the pathological roles of P. gingivalis proteases and review the scientific literature for bioactive plant-derived compounds endowed with a capacity to inhibit these enzymes.