Background: Hyperbaric oxygen therapy (HBOT) has been reported as an emerging treatment regimen for fibromyalgia syndrome (FMS), with a paucity of solid evidence. Accordingly, a systematic review and meta-analysis were performed to address the effectiveness of HBOT on FMS. Methods: We searched the Cochrane Database, EMBASE, Medline, PubMed, Clinicaltrials.gov, and PsycINFO, and the reference sections of original studies and systematic reviews from inception to May 2022. Randomized controlled trials (RCTs) on the treatment of FMS with HBOT were included. Outcome measures included pain, Fibromyalgia Impact Questionnaire (FIQ), Tender Points Count (TPC), and side effects. Results: Four RCTs, with 163 participants, were included for analysis. Pooled results showed that HBOT could benefit FMS with significant improvement at the end of treatment, including FIQ (SMD = −1.57, 95% CI −2.34 to −0.80) and TPC (SMD = −2.50, 95% CI −3.96 to −1.05). However, there was no significant effect on pain (SMD = −1.68, 95% CI, −4.47 to 1.11). Meanwhile, HBOT significantly increased the incidence of side effects (RR = 24.97, 95% CI 3.75 to 166.47). Conclusions: Collectively, emerging evidence from RCTs indicates that HBOT can benefit FMS patients in FIQ and TPC throughout the observation time phrases. Although HBOT has some side effects, it does not cause serious adverse consequences.