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Background: Patients with fibromyalgia experience chronic, widespread pain. It remains a misunderstood disorder with multimodal treatments providing mixed results. Objectives: To examine the effects of radial shockwave therapy (RSWT) compared to placebo on pain, pain catastrophizing, psychological indices, blood markers, and neuroimaging. Study-related experiences were also explored qualitatively. Methods: Quantitative sensory testing (QST), Visual Analog Scale (VAS), Beighton Scoring Screen (BSS), Pain Catastrophizing Scale (PCS), blood biomarker (Interleukin (IL)-6 and IL-10), and brain fMRI were measured pre- and post-treatment along with a post-treatment survey. The RSWT group received five treatments (one week apart over five-week period) to the three most painful areas (500 shocks at 1.5 bar and 15 Hz, then 1000 shocks at 2 bar and 8 Hz, and finally 500 shocks at 1.5 bar and 15 Hz) versus sham treatment for the placebo group. Results: There were no statistically significant differences in the BSS for hypermobility (p =.21; d =.74), PCS (p =.70; d =.22), VAS (p =.17–.61; d =.20–.83) scores, QST for skin temperature and stimuli (p =.14–.65; d =.25–.88), and for the pressure pain threshold (p =.71–.93; d =.05–.21). The VAS scores had clinically significant changes (MCID greater than 13.90) with improved pain scores in the RSWT group. Neuroimaging scans revealed no cortical thickness changes. Post-treatment surveys revealed pain and symptom improvements and offered hope to individuals. Conclusion: RSWT was implemented safely, without any negative treatment effects reported, and acted as a pain modulator to reduce sensitivity. Clinical Trials Registration: ClinicalTrials.gov identification number NCT02760212 [ABSTRACT FROM AUTHOR]