Metabolomic research tends to increase in popularity over the years, leading to the identification of new biomarkers related to specific health disorders. Saliva is one of the most newly introduced and systematically developed biofluids in the human body that can serve as an informative substance in the metabolomic profiling armamentarium. This review aims to analyze the current knowledge regarding the human salivary metabolome, its alterations due to physiological, environmental and external factors, as well as the limitations and drawbacks presented in the most recent research conducted, focusing on pre—analytical and analytical workflows. Furthermore, the use of the saliva metabolomic profile as a promising biomarker for several oral pathologies, such as oral cancer and periodontitis will be investigated.