Vascular dementia (VaD) is a type of dementia that results from brain injury caused by cerebrovascular disease or vascular risk factors. Accumulating evidence from clinical studies has found that Xixin decoction can effectively improve the cognitive function of patients with VaD and improve their daily living ability. However, the pathogenesis of VaD is not fully understood, and the therapeutic mechanism of Xixin decoction is also unclear. The Morris water maze, new object recognition, transmission electron microscopy observation, Golgi staining, Nissl staining, Western blotting, and quantitative real-time polymerase chain reaction were employed to explore the therapeutic mechanism of Xixin decoction. The results showed decreased learning and cognitive abilities, hippocampal neuron damage, decreased NPTX2 protein expression, and increased expression of inflammatory factors such as C1q and C3 in the model group compared with the control group. Furthermore, compared with the model group, the above symptoms were improved after administration of Xixin decoction, and the activity of the NPTX2/C1q/C3 complement pathway was altered. In conclusion, these results suggested that Xixin decoction might treat VaD by modulating the NPTX2/C1q/C3 complement pathway.