Periodontitis is a chronic inflammatory disease resulting from a dysbiosis of the dental biofilm and a dysregulated host response in susceptible individuals. It is characterized by periodontal attachment destruction, bone resorption, and eventual tooth loss. Salivary biomarkers have been sought to predict and prevent periodontitis. This comparative study analyzed the salivary proteome of 30 individuals with chronic periodontitis (CP) and 10 with periodontal health (PH), and correlated specific proteins with clinical parameters of disease by using mass spectrometry. Stimulated whole saliva was obtained and pooled for 5 healthy controls and 15 CP patients, precipitated with TCA, digested enzymatically with trypsin and analyzed by an LTQ Orbitrap Velos equipped with a nanoelectrospray ion source. A wide range of salivary proteins of various functions was significantly reduced in CP individuals, whereas salivary acidic proline-rich phosphoprotein, submaxillary gland androgen-regulated protein, histatin, fatty acid-binding protein, thioredoxin, and cystatin were predominant in diseased patients and correlated significantly with signs of periodontal attachment loss and inflammation. Specific salivary proteins were associated with PH and CP. These differences in salivary proteome profiles may contribute to the identification of disease indicators or signatures and the improvement of periodontal diagnosis.