Abstract: Objective To establish an Alzheimer disease (AD) cell model and explore whether salvianolic acid B (Sal B), a monomer from traditional Chinese herbal medicine, exerts protective effect and its underlying mechanisms. Methods SH-SY5Y human neuroblastoma cells were damaged using okadaic acid (OA) to construct a hyperphosphorylated Tau protein model. SH-SY5Y cells were divided into three groups: control group, OA model group, and OA + Sal B group. Cell viability was assessed using the CCK-8 assay, and cell morphological changes were observed under a microscope. Western blot was used to detect the levels of relevant proteins in cells. The level of reactive oxygen species (ROS) was measured using a ROS assay kit, and mitochondrial membrane potential was detected using a mitochondrial membrane potential assay kit. Results Compared with the control group, the OA model group showed weakened cell adhesion, irregular cell morphology, shortened and disappeared neurite-like structures, and a significant decrease in cell viability. The expression of phosphorylated Tau protein significantly increased in the OA model group. However, co-treatment with salvianolic acid B significantly reversed these changes. Furthermore, exposure to OA promoted the increase of ROS levels and loss of mitochondrial membrane potential in SH-SY5Y cells, while Sal B notably improved these effects. Conclusions Sal B may protect against OA-induced SH-SY5Y cell damage in the AD model through inhibiting ROS levels, maintaining mitochondrial membrane integrity, and other mechanisms.