Oral cancer (OC), the sixth most common cancer, is one of the leading public health problems worldwide, which is mainly represented by oral squamous cell carcinoma. Smoking and alcohol consumption are considered risk factors for OC. The major hindrance regarding OC is delayed diagnosis at the advanced clinical stages (i.e., III or IV), which affects its morbidity and mortality rates with a minimum 5-year survival rate of 20%–25%. Recurrences and metastasis often occur in more than 80% of patients within the first 2 years, even after primary treatment. Although a histological investigation is available as the gold standard of OC diagnosis, the application of noninvasive methods, including liquid biopsy, has been the focus of recent studies. In cancer diagnosis and health surveillance, saliva as a noninvasive and cost-effective bio-fluid containing several biomarkers, including metabolites, circulating tumor and tissue-derived cells, cytokines, DNA, RNA, and exosomes, has promising potential. Therefore, the improvement of salivary biomarkers is an utmost need for early cancer detection, particularly in the oral cavity and oropharynx, which gained the interest of most researchers and clinicians. The current review aimed to discuss the emerging issues of the most recent data on salivary biomarkers with particular attention to the potential early detection markers in OC. In addition, we report our previous findings on salivary biomarkers and their clinical significance as potentials in diagnosis, prognosis, and monitoring of OC.