Metabolomics is the systematic study of the unique chemical fingerprints of low molecular weight endogenous metabolites or metabolite profiles in a biological sample. Metabolites that are important indicators of physiological or pathological states can provide information for the identification of early and differential markers for disease and help to understand its occurrence and progression. Analysis of these key biomarkers has become an important role to monitor the state of biological organisms and is a widely used diagnostic tool for disease. Metabolomic analyses are propelling the field of medical diagnostics forward at unprecedented rates because of its ability to reliably identify metabolites that are at the metabolic level in concentration. These advancements have benefited biomarker research to the point where saliva is now recognized as an excellent diagnostic medium for the detection of disease. Saliva contains a large array of metabolites, many of which can be informative for the detection of diseases. Salivary diagnostics offer an easy, inexpensive, safe, and noninvasive approach for disease detection. Discovery of salivary biomarkers that could be used to scrutinize health and disease surveillance has addressed its diagnostic value for clinical applications. Availability of emerging metabolomic techniques gives optimism that saliva can eventually be placed as a biomedium for clinical diagnostics. Comprehensive salivary metabolome will be an important resource for researchers who are studying metabolite chemistry, especially in the fields of salivary diagnostics, and will be helpful for analyzing and hence identifying corresponding disease-related salivary biomarkers. This review presents an overview of the value of saliva as a credible diagnostic tool, the discovery of salivary biomarkers, and the development of salivary diagnostics now and in the future. In particular, proof of principle has been demonstrated for salivary biomarker research.