BACKGROUND: Recent evidence has suggested that reversal of gray or white matter abnormalities could be a criterion of recovery in patients with chronic pain. OBJECTIVE: To determine the effectiveness of exercise-based interventions in reversing gray and white matter abnormalities in patients with chronic musculoskeletal pain. METHODS: An electronic search was performed in the MEDLINE (Via PubMed), EMBASE, Web of Science, LILACS, SPORTDiscus, CINAHL, PEDro, and CENTRAL databases. Randomized clinical trials (RCTs) including patients with chronic musculoskeletal pain, which assessed the change in gray and white matter abnormalities after exercise-based interventions were selected. The risk of bias was assessed using the Risk of Bias II tool. RESULTS: Four RCTs were included (n= 386). Three studies showed reversal of abnormalities with exercise-based interventions compared to control groups. The reversal was observed in the gray matter volume in the medial orbital prefrontal cortex and in the supplementary motor area of patients with osteoarthritis, in the hippocampus, insula, amygdala and thalamus in fibromyalgia patients. Furthermore, in patients with chronic spinal pain, reversal was observed in the gray matter thickness of the frontal middle caudal cortex and in the caudate, putamen and thalamus gray matter volume. CONCLUSIONS: There is insufficient evidence to determine the effectiveness of exercise-based interventions for reversing gray and white matter abnormalities in patients with chronic pain. Further studies are still needed in this field.