Introduction: Post-concussion syndrome is common in young adults and can greatly interfere with the quality of daily life. It has a wide range of symptoms that require prompt and well-targeted treatment to avoid further brain impairment. Hyperbaric oxygen therapy (HBOT) is a promising regenerative treatment option for these patients to help prevent the progression of post-concussion syndrome. This study aims to determine whether HBOT accelerates the healing process and reduces symptoms in patients with post-concussion syndrome. Methods: 20 patients with post-concussion syndrome participated in this randomized controlled trial study. After receiving standard mild traumatic brain injury treatment in accordance with the Advanced Trauma Life Support guidelines, the patients were divided into HBOT and control groups. Matrix metallopeptidase 9 (MMP-9) levels and Rivermead Post-Concussion Symptoms Questionnaire (RPQ) scores were used to compare the two groups (before HBOT & after 1st, 3rd, and 5th week). Results: The study sample was predominantly male (65%) with an average age of 60 years old. HBOT reduced serum MMP-9 levels by nearly 20 ng/mL (p < 0.001) compared with the control treatment. The efficacy of HBOT was also reflected in the RPQ scores, which were significantly lower in the HBOT group than the control group (before HBOT & after 1st, 3rd, 5th week) (-3.80 on RPQ-3, p = p<0.001; -16.20 on RPQ-13, p = p<0.001). Conclusion: HBOT ameliorated the symptoms associated with post-concussion syndrome through a mechanism that involves MMP-9 activity. The accelerated recovery observed in the present study supports the use of HBOT to treat post-concussion syndrome and potentially other forms of traumatic brain injury.