LAUSR

&NA; Matrix metalloproteinase (MMP)‐12, S100A8/A9, and S100A12 are involved in innate immune responses. We addressed whether different aspects of oral health and non‐disease‐related covariates influence their levels in saliva. 436 participants were clinically examined, completed a health questionnaire, and provided stimulated saliva. Salivary levels of MMP‐12, S100A8/A9, and S100A12 were determined by enzyme‐linked immunosorbent assays. Lower MMP‐12 levels were observed in individuals 40–64 years old (yo) compared to < 40 yo, and higher S100A8/A9 levels were found in individuals > 64 yo compared to 40–64 yo. Smokers exhibited lower MMP‐12 and S100A12 levels compared to non‐smokers. All three proteins were elevated in individuals with bleeding on probing (BOP) > 20% compared to those with BOP ≤ 20%, and the S100A8/A9 levels were higher in individuals having ≥ 10% gingival pocket depths (PPD) ≥ 4 mm compared to the ones with shallow pockets < 4 mm. The extent of alveolar bone loss or presence of manifest caries did not alter any of the markers. MMP‐12, S100A8/A9, and S100A12 levels were higher in participants with high periodontal inflammatory burden. All three proteins correlated positively to BOP, PPD, and to several inflammatory mediators. The explanatory variables for MMP‐12 in saliva were age, smoking, presence of any tumor, and percentage of PPD ≥ 4 mm. The determinant of salivary S100A8/A9 was percentage of BOP, while S100A12 levels were associated with percentage of BOP and presence of any tumor. Taken together, MMP‐12 and the S100/calgranulin levels in saliva reflect different aspects of periodontal inflammation. Smoking and age should be taken into account in further investigation of these proteins as biomarker candidates of periodontal disease.