Because of the irreversible nature of periodontal disease, early diagnosis is an important aspect of management of patients with periodontal disease. Human saliva is an attractive medium for disease diagnosis because its collection is noninvasive and simple. Analysis of saliva may be especially beneficial in the determination of current periodontal status and serve as means for the screening of periodontal disease. In the present study, we investigated potential biochemical markers in whole saliva samples for the screening of periodontal disease using proteomics technique. We enrolled five subjects each from four different groups on the basis of measures of periodontal health (healthy group, gingivitis group, chronic periodontitis group and aggressive periodontitis group). Eleven proteins in whole saliva samples were identified as differentially expressed proteins between the healthy and periodontal disease groups using 2-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight / time-of-flight mass spectrophotometry (MADLI-TOF/TOF MS) approaches. Although the diagnostic value of oral fluid has been recognized for some time and potential biomarkers of periodontal disease have been identified in saliva, this, to our knowledge, is one of the first studies to examine large-scale proteomic profiling to identify the extent of periodontal destruction. Thus, this work provides an important framework for future efforts aimed at understanding salivary responses to periodontal destruction and predicting the future disease progression.