There is a lack of knowledge about the efficacy of manual therapy (MT) on subjects with temporomandibular disorders (TMD). The objective of this systematic review is to synthetise evidence that regards the isolated effect of MT in improving maximum mouth opening (MMO) and pain in subjects with signs and symptoms of TMD. MEDLINE , Cochrane, Web of Science, SciELO and EMBASE electronic databases were consulted, searching for randomised controlled trials applying MT for TMD compared to other intervention, no intervention or placebo. Two authors independently extracted data, PEDro scale was used to assess risk of bias, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) was applied to synthetise overall quality of the body of evidence. Treatment effect size was calculated for pain, MMO and pressure pain threshold (PPT). Eight trials were included, seven of high methodological quality. Myofascial release and massage techniques applied on the masticatory muscles are more effective than control (low to moderate evidence) but as effective as toxin botulinum injections (moderate evidence). Upper cervical spine thrust manipulation or mobilisation techniques have greater efficacy than control (low to high evidence), while thoracic manipulations are not. There is moderate-to-high evidence that MT techniques protocols are effective. The methodological heterogeneity across trials protocols often contributed to a reduced quality of evidence. In conclusion, there is widely varying evidence that MT improves pain, MMO and PPT in subjects with TMD signs and symptoms, depending on the technique. Further studies should consider using standardised evaluations and better study designs to strengthen clinical relevance.