A biomimetic self-propelled nanomotor with cascade targeting capacity was developed for the treatment of neurological inflammatory diseases. The nanomotor features an asymmetric structure with a mesoporous SiO₂ head and multiple MnO₂ tentacles, mimicking macrophage membranes to enable inflammatory targeting and BBB penetration. The MnO₂ agents catalyze the degradation of H₂O₂ into O₂, reducing brain inflammation and providing propulsion for deep brain penetration. The mesoporous SiO₂ head is loaded with curcumin, which regulates macrophage polarization from M1 to M2, enhancing anti-inflammatory effects. In vitro and in vivo experiments confirmed the nanomotor's ability to precisely target brain injury sites, penetrate deep into brain tissue, and reduce inflammation while maintaining nervous system function. The nanomotor's self-propelled motion, driven by oxygen bubbles generated from H₂O₂, allows it to navigate through complex brain tissue. The biomimetic design enables the nanomotor to cross the BBB and accumulate in inflamed regions. The nanomotor also exhibits enzyme-like activities, scavenging ROS and promoting microglial polarization from M1 to M2. In vivo studies showed that the nanomotor significantly improved behavioral recovery and spatial learning in TBI mice, reduced brain water content, and enhanced cognitive function. The nanomotor demonstrated excellent biocompatibility and safety, with no significant organ toxicity or systemic adverse effects. This study introduces a promising platform for targeted anti-inflammatory therapy in neurological diseases, offering a novel approach for effective treatment of brain inflammation.A biomimetic self-propelled nanomotor with cascade targeting capacity was developed for the treatment of neurological inflammatory diseases. The nanomotor features an asymmetric structure with a mesoporous SiO₂ head and multiple MnO₂ tentacles, mimicking macrophage membranes to enable inflammatory targeting and BBB penetration. The MnO₂ agents catalyze the degradation of H₂O₂ into O₂, reducing brain inflammation and providing propulsion for deep brain penetration. The mesoporous SiO₂ head is loaded with curcumin, which regulates macrophage polarization from M1 to M2, enhancing anti-inflammatory effects. In vitro and in vivo experiments confirmed the nanomotor's ability to precisely target brain injury sites, penetrate deep into brain tissue, and reduce inflammation while maintaining nervous system function. The nanomotor's self-propelled motion, driven by oxygen bubbles generated from H₂O₂, allows it to navigate through complex brain tissue. The biomimetic design enables the nanomotor to cross the BBB and accumulate in inflamed regions. The nanomotor also exhibits enzyme-like activities, scavenging ROS and promoting microglial polarization from M1 to M2. In vivo studies showed that the nanomotor significantly improved behavioral recovery and spatial learning in TBI mice, reduced brain water content, and enhanced cognitive function. The nanomotor demonstrated excellent biocompatibility and safety, with no significant organ toxicity or systemic adverse effects. This study introduces a promising platform for targeted anti-inflammatory therapy in neurological diseases, offering a novel approach for effective treatment of brain inflammation.