Traumatic brain injury (TBI) is one of the leading causes of fatality and disability worldwide. Despite its high prevalence, effective treatment strategies for TBI are limited. Traumatic brain injury induces structural and functional alterations of astrocytes, the most abundant cell type in the brain. As a way of coping with the trauma, astrocytes respond in diverse mechanisms that result in reactive astrogliosis. Astrocytes are involved in the physiopathologic mechanisms of TBI in an extensive and sophisticated manner. Notably, astrocytes have dual roles in TBI, and some astrocyte-derived factors have double and opposite properties. Thus, the suppression or promotion of reactive astrogliosis does not have a substantial curative effect. In contrast, selective stimulation of the beneficial astrocyte-derived molecules and simultaneous attenuation of the deleterious factors based on the spatiotemporal-environment can provide a promising astrocyte-targeting therapeutic strategy. In the current review, we describe for the first time the specific dual roles of astrocytes in neuronal plasticity and reconstruction, including neurogenesis, synaptogenesis, angiogenesis, repair of the blood-brain barrier, and glial scar formation after TBI. We have also classified astrocyte-derived factors depending on their neuroprotective and neurotoxic roles to design more appropriate targeted therapies. Video Abstract.