Temporomandibular Disorders (TMD) represent a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles and/or associated structures. They are a major cause of non-dental orofacial pain. As a group, they are often multi-factorial in nature and have no common etiology or biological explanations. TMD can be broadly divided into masticatory muscle and TMJ disorders. TMJ disorders are characterized by intra-articular positional and/or structural abnormalities. The most common type of TMJ disorders involves displacement of the TMJ articular disc that precedes progressive degenerative changes of the joint leading to osteoarthritis (OA). In the past decade, progress made in the development of stem cell-based therapies and tissue engineering have provided alternative methods to attenuate the disease symptoms and even replace the diseased tissue in the treatment of TMJ disorders. Resident mesenchymal stem cells (MSCs) have been isolated from the synovia of TMJ, suggesting an important role in the repair and regeneration of TMJ. The seminal discovery of pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have provided promising cell sources for drug discovery, transplantation as well as for tissue engineering of TMJ condylar cartilage and disc. This review discusses the most recent advances in development of stem cell-based treatments for TMJ disorders through innovative approaches of cell-based therapeutics, tissue engineering and drug discovery.