The heavy burden of oral diseases such as oral cancers, dental caries, periodontitis, etc. and their consequence on the patient’s quality of life demonstrated an urgent demand for developing effective therapeutics. Quercetin as a natural derived flavonoid, could be utilized in the therapeutic formulation of various diseases such as diabetes, breast cancer and asthma, owing to its prominent pharmacological values. In the last decade, the applications of quercetin as a natural compound in oral treatment have attracted increasing interest due to its multifunction including antioxidant, antibacterial, anti-inflammatory and antineoplastic activities. Besides, considering the low bioavailability of quercetin, great efforts have been made in its drug delivery systems to address the problem of limited application. Therefore, this review summarized the cutting-edge researches on versatile effects and enhanced bioavailability of quercetin resulting from innovative drug delivery systems, particularly focused on its potential against oral diseases. The application of quercetin would provide novel and promising therapeutic approach for clinical treatment, promoting the development of global dental public health.