Background: This systematic review and meta-analysis aimed to update and give an overview of the evidence from published literature that focused on the efficacy of cognitive behaviour therapy (CBT) in the management of somatoform disorders and medically unexplained physical symptoms (MUPS). Methods: A comprehensive literature search was carried out through an electronic search of various databases on randomized controlled trials (RCTs). Primary outcome was the severity of somatic symptoms. Secondary outcomes were also measured based on severity of anxiety symptoms, severity of depressive symptoms, social functioning, physical functioning, doctor visits and the compliance with CBT, as well as follow-up visits. Effects were summarized by a random effects model using mean differences or odds ratio with 95% confidence intervals (CIs). Results: A total of 15 RCTs comprising 1671 patients with somatoform disorders or MUPS were enrolled in our systematic review and meta-analysis. The main analysis revealed that CBT could alleviate somatic symptoms: −1.31 (95% CI: −2.23 to −0.39, p = 0.005); anxiety symptoms: -1.89 (95% CI: −2.91 to −0.86; p < 0.001); depressive symptoms: −1.93 (95% CI: −3.56 to −0.31; p = 0.020); improve physical functioning: 4.19 (95% CI: 1.90 to 6.49; p < 0.001). The efficacy of CBT on alleviating somatic symptoms, anxiety and depressive symptoms were sustained on follow-up. CBT may not be effective in reducing the number of doctor visits: −1.23 (95% CI: −2.97 to 0.51; p = 0.166); and improving social functioning: 3.27 (95% CI: −0.08 to 6.63; p = 0.056). The results of subgroup analysis indicated that CBT was particularly beneficial when the duration of session was more than 50 min to reduce the severity of somatic symptoms from pre to post treatment time, when it was group based and applied affective and developed good interpersonal strategy during the treatment. Longer duration and frequency such as more than 10 sessions and 12 weeks treatments had significant effect on reduction of the comorbid symptoms including depression and anxiety, but they may underpin low level of compliance of CBT based treatments. Conclusions: CBT is effective for the treatment of somatoform disorders and MUPS by reducing physical symptoms, psychological distress and disability.