Human saliva is a complex secretion containing abundance of biomolecules derived from salivary glands, mucosal and periodontal tissues, and oral microorganisms. Formation of saliva is involved with coupling of the nerve-mediated reflex to glandular secretion of salivary fluid and proteins. A variety of molecules including peptides, proteins, glycoprotein, lipids, metabolites, RNA, and genomic DNA can be found in saliva. These salivary molecules are derived from both local and
systemic sources. Saliva has multifunctional roles in maintenance of oral health and supplies a variety of physiologically systemic needs including protection against tooth demineralization and microbial invasion, tissue lubrication, food perception, food digestion, and wound healing. Saliva can be an alternative source of other biofluids, because of the ease of obtainment, non-invasiveness and safety, and pleasantness of use. With an advanced-high throughput technology, a potential use of saliva as a diagnostic tool for oral and systemic diseases becomes essential for laboratory and clinical investigations with the aim of using saliva as a possible complementary examination with routinely diagnostic methods. The term “Salivaomics” was established recently to describe the information derived from studies in human saliva including: genomics and epigenomics, transcriptomics, proteomics, metabolomics and microbiomics. The aim of this review was to update the knowledge of human saliva regarding its role in oral and systemic health and diseases.