Periodontal disease is driven by oral pathogens like P. gingivalis and inflammatory cytokines, which interact with ADAM proteins. By analyzing patients' gingival crevicular fluid, this study demonstrated that ADAM8 expression and activity correlate directly with disease severity, whereas ADAM10 correlates inversely. The findings conclude that the dysregulation of ADAM proteolytic activity is a key driver in periodontal disease progression, highlighting the targeting of ADAM8 as a promising and novel local therapeutic option for future translational studies