Abstract: Background: Pain management is one of the main parts of treatments for Temporomandibular Disorders (TMDs). However, there is still a lack of high-quality evidence that compare the overall effects of these non-surgical treatments. The objective of this systematic review is to identify the most potential treatment protocol in dealing with pain caused by TMDs through a mixed comparison of interventions based on network meta-analysis. Methods: A systematic review and network meta-analysis of studies identified by searching PubMed, Embase, Medline, Ovid, and CINAHL. All the included studies should have characteristics that: (1) participants with TMDs of any age; (2) non-surgical treatments; (3) score of Visual Analog Scale (VAS) as the outcome measure; (4) randomized controlled trials. The Cochrane Bias Assessment Toll was used to assess the bias, the CINeMA website was applied to rate the confidence of evidence, and ADDIS software was used to conduct the network meta-analysis. Results: 46 studies were included in this review. The agreement between authors reached a kappa value of 0.78. The results of the network meta-analysis showed that wearable therapy devices are more likely to be the best choice for reducing the pain of patients with myogenic TMDs, whereas a combination of platelet-rich plasma injection and wearable therapy devices is more likely to be the best choice for reducing the pain in a long term after treatment for patients with mix-type TMDs. Moreover, the application of therapy equipment has the most potential in reducing pain in a long term after treatment for patients with articular TMDs. Discussion: Wearable devices have a great potential for pain syndrome caused by TMDs, the mechanism might come from a biomechanical perspective. However, the overall confidence rating of evidence is low. Studies with high quality are still needed in the future. Other: The PROSPERO Registration Number of this systematic review is CRD42021253442.