Y‐maze and object recognition tests showed that the synthesized NPs significantly improved spatial memory in AD transgenic mice. Furthermore, these NPs reduced amyloid‐β levels, reactive oxygen species (ROS), and anti‐inflammatory biomarkers (i.e., TNF‐α and IL‐6). Along with these benefits, the S1 and curcumin loaded PLGA NPs functionalized with CRT restored optimal superoxide dismutase activities and facilitated synaptogenesis in AD mouse brains. This evidence concerns the gene TNF and Alzheimer disease.