Traumatic brain injury (TBI) generates excess reactive oxygen species (ROS), which can exacerbate secondary injury and result in disability and death. Secondary injury cascades can trigger the release of uncontrolled ROS into the surrounding normal brain tissue, forming an extended pool of ROS, which leads to massive neuronal death. Here, we developed an injectable, post-trauma microenvironment-responsive, ROS depletion hydrogel embedded curcumin (Cur) (TM/PC) for reducing ROS levels in damaged brain tissue to promote the regeneration and recovery of neurons. Hydrogel was composed of three parts: (1) Hydrophobic poly (propylene sulfide)120 (PPS120) was synthesized, with a ROS quencher and H2O2-responsive abilities, to embed Cur. (2) Matrix metalloproteinase (MMP)-responsive triglycerol monostearate (TM) was used to cover the PPS120 to form a TM/P hydrogel. (3) Cur could further eradicate the ROS, promoting the regeneration and recovery of neurons. In two postoperative TBI models, TM/PC hydrogel effectively responded the TBI surgical environment and released drug. TM/PC hydrogel significantly depleted ROS and reduced brain edema. In addition, reactive astrocytes and activated microglia were decreased, growth-associated protein 43 (GAP43) and doublecortin (DCX) were increased, suggested that TM/PC hydrogel had the strongest anti-inflammatory effect and effectively promoted nerve regeneration after TBI. This study provides new information for the management of TBI to prevent the secondary spread of damage.