This work was conducted to prepare beta-caryophyllene-hydroxypropyl-beta-cyclodextrin inclusion complex (HP beta CD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats. First, HP beta CD/BCP was prepared, optimized, characterized, and evaluated. HP\CD/BCP and AM630 were then administered to VD rats to upregulate and downregulate the cannabinoid receptor type 2 (CB2). Results showed that HP beta CD/BCP can significantly increase the bioavailability of BCP. Through the Morris water maze test, HP beta CD/BCP can attenuate learning and memory deficits in rats. Cerebral blood flow (CBF) monitoring results indicated that HP beta CD/BCP can promote the recovery of CBF. Moreover, molecular biology experiments showed that HP beta CD/BCP can increase the expression levels of CB2 in brain tissues, particularly the hippocampus and white matter tissues, as well as the expression levels of PI3K and Akt. Overall, the findings demonstrated the protective effects of HP beta CD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HP beta CD/BCP in the therapy of vascular dementia in the future.