In conclusion, our results revealed that 1,25-D3 can activate VDR to affect angiogenesis, activate the AMPK/AKT/GSK-3β pathway, inhibit apoptotic proteins p53, CytC, and caspase-3, regulate mitochondrial metabolic function, reduce the levels of ROS and MDA, and increase the activity of ATPase and SDH, which ultimately had a protective effect on stroke. This evidence concerns the gene GSK3B and Stroke.