Hybrid cell membrane-coated nanoparticles offer a promising approach for targeted therapy in Alzheimer's disease (AD). The blood-brain barrier (BBB) limits the delivery of therapeutic drugs to the brain, but hybrid nanoparticles derived from different cell types can mimic the surface properties of their source cells, enhancing targeting precision and therapeutic efficacy. This study designed a novel hybrid cell membrane coating by combining platelet membranes with those overexpressing the CCR2 receptor, enabling the nanoparticles to cross the BBB and target neuroinflammatory lesions. Two drugs with different mechanisms—rapamycin (autophagy enhancer) and TPPU (soluble epoxide hydrolase inhibitor)—were loaded into liposomes to achieve multitargeted therapy. In a transgenic mouse model of familial AD (5xFAD), these drug-loaded hybrid liposomes significantly reduced amyloid plaque deposition, neuroinflammation, and cognitive impairments. The hybrid cell membrane-coated nanomaterials demonstrated enhanced BBB penetration and targeted delivery to inflammatory lesions in the brain. In vitro and in vivo experiments showed that the hybrid liposomes improved cell viability, reduced pathological protein burden, and alleviated neuroinflammation. The results indicate that hybrid cell membrane-coated nanoparticles represent a versatile platform for targeted therapy in AD, offering new opportunities for precise drug delivery and disease-specific targeting. This approach could lead to more effective and personalized treatments for AD and other neurological disorders.Hybrid cell membrane-coated nanoparticles offer a promising approach for targeted therapy in Alzheimer's disease (AD). The blood-brain barrier (BBB) limits the delivery of therapeutic drugs to the brain, but hybrid nanoparticles derived from different cell types can mimic the surface properties of their source cells, enhancing targeting precision and therapeutic efficacy. This study designed a novel hybrid cell membrane coating by combining platelet membranes with those overexpressing the CCR2 receptor, enabling the nanoparticles to cross the BBB and target neuroinflammatory lesions. Two drugs with different mechanisms—rapamycin (autophagy enhancer) and TPPU (soluble epoxide hydrolase inhibitor)—were loaded into liposomes to achieve multitargeted therapy. In a transgenic mouse model of familial AD (5xFAD), these drug-loaded hybrid liposomes significantly reduced amyloid plaque deposition, neuroinflammation, and cognitive impairments. The hybrid cell membrane-coated nanomaterials demonstrated enhanced BBB penetration and targeted delivery to inflammatory lesions in the brain. In vitro and in vivo experiments showed that the hybrid liposomes improved cell viability, reduced pathological protein burden, and alleviated neuroinflammation. The results indicate that hybrid cell membrane-coated nanoparticles represent a versatile platform for targeted therapy in AD, offering new opportunities for precise drug delivery and disease-specific targeting. This approach could lead to more effective and personalized treatments for AD and other neurological disorders.