Oral and maxillofacial (OMF) defects caused by congenital conditions and various injuries such as trauma, warfare, ablative surgery for benign and malignant head & neck tumor can often lead to OMF deformities and malfunctions in speech, mastication/chewing, and swallowing as well as deleterious psychological effects and socioeconomic burdens to patients. Due to the unique complex 3D geometry and complicated causes, reconstruction and rehabilitation of OMF defects remain a major challenge for OMF surgeons. Currently, microsurgical free tissue transfer remains the mainstay of care in the reconstruction of OMF defects due to their abundant blood supply and flexibility for transplantation. However, there exists several major challenges, such as the limited availability, the requirement of a secondary surgery and donor site morbidity, and the multifactorial failure of free flap transplantation. Due to the advancement in stem cell biology, biomaterial science, and tissue engineering (TE) technology, stem cell-based regenerative therapy is emerging as a promising therapeutic approach for a variety of diseases, including regenerative reconstruction and rehabilitation of OMF defects. In this narrative review, we update the information on the characteristics and biological functions of mesenchymal stem cells derived from various dental tissues (dental-MSCs) and their released cell-free products, extracellular vesicles (EVs). We then highlight their potential application in TE and regenerative reconstruction of OMF defects in animal models and clinical studies and the potential challenges in this field.