Trappin-2 is a potent biologically active serine protease inhibitor with anti-inflammatory properties that has also been characterized as an "alarm anti-protease." Although the importance of trappin-2 in several chronic infections has been demonstrated, its potential involvement in periodontitis remains undefined. This study aims to investigate salivary levels of trappin-2 and interleukin (IL)-1β in periodontally healthy individuals and patients with gingivitis or generalized chronic periodontitis (CP) or aggressive periodontitis (GAgP). Whole unstimulated saliva samples were collected from 80 systemically healthy and non-smoking individuals before full-mouth periodontal examination. Trappin-2 and IL-1β were analyzed by enzyme-linked immunosorbent assay and reported as nanograms per milligram after calibration for total protein levels. Correlation analysis revealed negative association between trappin-2 and IL-1β levels. Trappin-2 also showed strong negative correlation with clinical periodontal parameters, in contrast to IL-1β, which showed positive correlation. Trappin-2 levels were significantly lower in individuals with CP and GAgP, but not gingivitis, compared with healthy individuals. Reduced salivary concentrations of trappin-2 had high sensitivity and specificity to distinguish health from periodontitis. Trappin-2 is abundant in the saliva of individuals with healthy periodontium in line with its role as an "anti-alarm" protease. Decreased salivary trappin-2 and increased IL-1β levels in individuals with periodontitis, compared with healthy individuals, may implicate a potential antiprotease/proinflammatory cytokine imbalance, resulting in impaired host protective capacity.