Porphyromonas gingivalis is the key etiological pathogen of periodontal disease, a chronic oral inflammatory condition that affects over 14% of the global population. P. gingivalis possesses several potent virulence factors—including gingipains, hemagglutinins, and fimbriae—that drive microbial dysbiosis. To restore homeostasis, nitric oxide (NO) is endogenously produced by immune cells to eliminate the infection[HL1.1], but disease persistence necessitates the use of therapeutic agents. The multiple antibacterial mechanisms of NO minimize the potential for antimicrobial resistance compared to traditional antibiotics, making exogenous NO delivery a potential attractive strategy for combating P. gingivalis. The objective of this study was to evaluate the effect of exogenous NO on the virulence of P. gingivalis, including NO’s capacity to influence biofilm formation and dispersion, invasion of host cells, mitigation of immune response, and gingipain activity and production. Nitric oxide effectively modulated the virulent behavior of P. gingivalis by reducing the pathogen’s ability to form biofilms and invade host cells. Nitric oxide exposure also altered the pathogen’s ability to export gingipains, thereby significantly reducing its pathogenicity. This work highlights the therapeutic potential of exogenous NO to alter periodontal disease through its multimodal effects on the virulence of P. gingivalis.