Advances in the use of saliva as a diagnostic fluid have been affected by current technological developments: enzyme–linked fluorescence technique, Western blot assays, polymerase chain reaction (PCR). Salivary diagnostics is a dynamic and emerging field utilizing nanotechnology and molecular diagnostics to aid in the diagnosis of oral and systemic diseases and using the salivary biomarkers for disease detection. With a salivary specimen, one can collect multiple specimens from the same individual at the optimum times for diagnostic information. Saliva can be considered as gland–specific saliva and whole saliva. Whole saliva is a mixed fluid that is derived predominantly from major and minor salivary glands. Analysis of saliva done for the diagnosis of  Hereditary disease, Autoimmune disease, Malignancy, Infection, Monitoring of levels of hormones and drugs, Bone turnover marker in saliva, Forensic Evidence, Dental caries and periodontal disease and in diagnosis of Oral Disease with Relevance for Systemic Diseases. This paper aims to impart and share knowledge on the role of saliva in diagnosis of oral and systemic disease using nanotechnology.