Background Temporomandibular disorder (TMD) is a condition, in which multiple factors act synergistically to determine the outcome of the disorder. Aim A systematic review and meta‐analysis was conducted to evaluate the association between genetic polymorphisms in catechol‐O‐methyltransferase (COMT) and TMD. Design Observational studies that investigated this association were included. The risk of bias and study quality were evaluated according to the Newcastle‐Ottawa tool. The meta‐analysis was performed for each polymorphism associated with TMD signs and symptoms. Results A total of 1903 articles were identified. Ten remained in the qualitative analysis: six were classified as low risk of bias and four with moderate risk of bias, and three were included in the meta‐analysis. The polymorphism rs6269, in the genotypic model (0.65; CI = 0.44‐0.97; P = .04) and in the allelic model (0.73; CI = 0.54‐0.98; P = .04), was associated with myofascial pain. The rs9332377 was associated with myofascial pain in the genotypic model (2.69; CI = 1.51‐4.76; P = .0007) and in the allelic model (1.46; CI = 1.01‐2.13; P = .05) and with painful TMD in the genotypic model (2.08; CI = 1.27‐3.40; P = .004) and in the allelic model (1.34 CI = 0.98‐1.82; P = .06). Conclusion The polymorphisms in COMT were significantly associated with TMD.