BACKGROUND AND AIM: Early detection of premalignant oral lesions, especially in high-risk patients, is important to prevent mortality. Dysplastic changes are one of the elements of premalignant lesions which can be perceived in histopathologic examinations. The use of saliva is a promising method for diagnosing epithelial dysplasia, because it is non-invasive and easy to collect. This review evaluated the salivary biomarkers in patients with oral epithelial dysplasia (OED).METHODS: In this systematic review study, all English articles were searched in the PubMed, Cochrane Library, Web of Science, and Scopus databases until February ۲۰۲۱. The searches were done using the Medical Subject Heading (MeSH) terms and free keywords. Textual data were analyzed manually and significant differences in salivary levels of biomarkers between patients with dysplastic lesions and healthy controls were reported and analyzed.RESULTS: Originally, ۱۷۲۶ articles were found, of which ۱۷ case-control articles were selected according to the inclusion/exclusion criteria. In ۸۵% of studies, proinflammatory cytokine levels were significantly increased in the groups with epithelial dysplasia compared to the control groups. Tumor necrosis factor-α (TNF-α), interleukin (IL)-۶, and IL-۱α showed an increase in all OED cases, but IL-۱β showed no significant difference between epithelial dysplasia and control groups. Salivary levels of ۱۴ types of micro-ribonucleic acid (miRNA) were studied, the most important of which were miRNAs ۲۱ and ۳۱, indicating a significant increase in the epithelial dysplasia groups compared to the control groups.CONCLUSION: Based on the results of this systematic review, evaluation of salivary cytokines (TNF-α, IL-۶, and IL-۱α) and miRNAs ۲۱ and ۳۱ may be a non-invasive method in the early detection and prognosis of epithelial dysplasia and may also be useful in developing new prevention and treatment strategies.