Objective To observe the effects of total saponins of Trillium tschonoskii Maxim (TST) on vascular cognitive impairment (VCI), neurovascular units (NVUs), and neural circuit integrity in rats. Methods Forty-eight male Sprague-Dawley (SD) rats were randomly divided into sham-operated group, model group, TST group (intragastric administration, 100 mg/kg), and donepezil group (intragastric administration, 0.45 mg/kg), and then subjected to ischemic stroke by 2-VO method (bilateral common carotid artery ligation) or sham surgery. After 28 days of intragastric administration, Mirros water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group. HE and Nissl staining were used to observe the pathological changes of brain tissue in rats. The expression of synuclein (SYN) in rat hippocampus was observed by immunohistochemical staining. Changes in dendritic spines in rat's hippocampal neurons were observed by Golgi staining. Western blotting was used to detect the expression levels of IL-1β, IL-10, vascular endothelial growth factor A (VEGFA), postsynaptic density protein 95 (PSD95), and growth associated protein 43 (GAP43) in rat's hippocampus in each group. Results In Mirros water maze test, rats in model group showed significant prolonged escape latency (P<0.05), and a significant reduction in the number of crossing platforms and the percentage of activity time in the target quadrant (P<0.05) than those in sham-operated group; while rats in TST group and donepezil group showed significant shortened escape latency (P<0.01), and significant increase of the number of times of crossing platforms and the percentage of activity time in the target quadrant (P<0.05) than those in model group. Compared of sham-operated group, model group showed a decrease in the expression of SYN and the number of neurons, Nissl bodies, and dendritic spines in the CA1 region of the hippocampus (P<0.05). Compared with model group, TST group and donepezil group showed an increase in the expression of SYN and the number of neurons, Nissl bodies, and dendritic spines in the CA1 region of the hippocampus (P<0.05). Western blotting showed a significant increase in the expression of IL-1β and VEGF (P<0.05), and a decrease in the expression of IL-10, PSD95, and GAP43 (P<0.01) in rat's hippocampus of model group than those in sham-operated group. Compared with model group, TST group and donepezil group showed a significant decrease in the expression of IL-1β (P<0.05), and an increase in the expression of VEGFA, IL-10, and GAP43 (P<0.05). Conclusions TST could alleviate cognitive impairment through promoting synaptic plasticity and neurovascular unit remodeling in 2-VO model rats, suggesting its significance as a potential drug for apoplexy.