Background: This systematic review of the literature was to compare the effects of exercise therapy and occlusal splint therapy on pain and mobility in individuals with painful temporomandibular disorders (TMD). Methods: PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched for English publications from database root to March 1, 2020. Search terms were [(“temporomandibular joint disorders” or “temporomandibular disorders” or “craniomandibular disorders” or “orofacial pain” or “myofascial pain” or “myofascial pain” or “facial pain”) AND (exercise or “physical therapy modalities” or physiotherapy or “exercise therapy”) AND (“splints” or “occlusal splints” or “stabilization splint” or “occlusal appliance” or “occlusal splint therapy”)]. We included randomized controlled trials that evaluated the effects of therapeutic exercise therapy and occlusal splint therapy, and were published in English. Trial quality was assessed with the Physiotherapy Evidence Database scale. Results: Six studies were included (498 patients: 251 occlusal splint therapy, 247 therapeutic exercise). The results revealed that exercise therapy was not superior to occlusal splint therapy for pain reduction in patients with painful TMD (P=0.08; weighted standardized mean difference −0.29; 95% CI, −0.62 to 0.04). The effectiveness of occlusal splint therapy and exercise therapy was found to be equivalent in the maximum mouth-opening range (P=0.51; weighted standardized mean difference 0.12; 95% CI, −0.24 to 0.48), right laterotrusion (P=0.99; weighted standardized mean difference −0.00; 95% CI, −0.31 to 0.31), left laterotrusion (P=0.32; weighted standardized mean difference 0.16; 95% CI, −0.16 to 0.48), and protrusion (P=0.77; weighted standardized mean difference 0.06; 95% CI, −0.32 to 0.43) for painful TMD patients. Conclusions: Given the limitations of the study, the small number of studies included in the sub-analysis for pain relief and the maximum mouth-opening range, and the small overall standardized mean difference for pain relief and mandibular movement observed, no high-quality evidence was found to distinguish the clinical effectiveness between occlusal splint therapy and exercise therapy for painful TMD patients. It appears that more randomized controlled trials comparing the effects of exercise therapy and occlusal splint therapy need to be implemented