<p>Traumatic brain injury (TBI) is a leading cause of mortality and long-term disability worldwide, with secondary injuries amplifying neuronal damage through mechanisms such as ferroptosis—a regulated iron-dependent cell death driven by lipid peroxidation. This review synthesizes current evidence on ferroptosis in TBI, highlighting its core pathways: (1) iron metabolism dysregulation (e.g., TfR1 upregulation, ferritin suppression), (2) lipid peroxidation (mediated by ACSL4/LPCAT3/PUFA oxidation), and (3) glutathione depletion (via System X_c^–/GSH/GPX4 axis disruption). Ferroptosis intersects with mitochondrial dysfunction, ER stress, and neuroinflammation, exacerbating neuronal death. The hippocampus, vulnerable to post-TBI damage, shows elevated ferroptosis markers (e.g., Tyro3, NRF2/p53 pathways). Iron chelators (e.g., deferoxamine), antioxidants (e.g., ferrostatin-1, liproxstatin-1), and natural compounds (e.g., melatonin, trehalose) demonstrate neuroprotection by mitigating oxidative stress and restoring metabolic balance. Emerging approaches include ncRNA therapies (e.g., miR-212-5p) and stem cell interventions targeting ferroptosis-related genes. Despite progress, key gaps persist in understanding ferroptosis crosstalk with apoptosis/pyroptosis, optimizing drug delivery (e.g., nanoparticle carriers), and validating biomarkers for clinical translation. Targeting ferroptosis offers a promising avenue for TBI treatment, but further research is needed to refine therapeutic specificity and integrate these strategies into clinical practice.</p>