Traumatic brain injury (TBI) is a structural and physiological disruption of brain function caused by external forces. It is the leading cause of death and disability worldwide. TBI includes both primary and secondary injuries. Excessive iron accumulation and ferroptosis are highly involved in the pathophysiological process of secondary brain injury. Ferroptosis is a form of regulatory cell death, characteristic as increased iron accumulation, lipid peroxidation, reactive oxygen species (ROS) production, mitochondrial dysfunction and neuroinflammatory responses, resulting in cellular and neuronal damage. For this reason, eliminating factors like excessive accumulation of iron and inhibiting lipid peroxidation may be a promising therapy approach. Iron chelators can be used to eliminate excess iron and to alleviate some of the clinical manifestations of TBI. In this review, we will focus on the mechanisms of iron and ferroptosis involved in the manifestations of TBI, broadening our understanding of the use of iron chelators for TBI. Through this review, we can better seek new research directions for further treatment of TBI.