Objective <p>Brain-derived neurotrophic factor (BDNF) is a critical blood protein for brain function; however, its genotypic influence on clinical outcomes and brain structure following mild traumatic brain injury (mTBI) remains unclear. This study investigated the relationship between BDNF polymorphisms and cognitive impairment, symptom severity, and cortical structural injury in mTBI patients.</p> Materials and methods <p>Sixty-one mTBI patients underwent neuropsychological assessments and MRI scans within one week post-injury, with 46 patients followed up at one month. Fifty-two healthy controls were included for comparison. Patients with mTBI exhibited clinical symptoms, cognitive impairment, and alterations in cortical thickness during in the acute phase.</p> Results <p>BDNF Met gene carriers (<i>n</i> = 41) and Val gene carriers (<i>n</i> = 20) demonstrated different cognitive performance in the acute phase and exhibited distinct recovery trajectories. Val carriers showed significantly better cognitive flexibility compared to Met carriers (<i>p</i> = 0.028) during the acute phase and greater improvement in clinical symptoms at one month (<i>p</i> = 0.035). Follow-up MRI scans revealed more extensive and statistically significant alterations in cortical thickness in Met carriers than in Val carriers (<i>p</i> &lt; 0.01), particularly in regions associated with cognitive and emotional regulation.</p> Conclusion <p>These findings suggest that BDNF polymorphisms in mTBI patients are associated with brain structural changes and may serve as valuable biomarkers for identifying individuals at risk for long-term clinical symptoms and cognitive impairment.</p>