Transient global cerebral ischemia (TGCI) induces by bilateral common carotid artery occlusion (BCCAO), and it mediates neuronal cell death of the CA1 hippocampal area. AM251 is a cannabinoid receptors type 1 (CB1) blocker that has been known to be protective against transient focal cerebral ischemia. JWH-015 is a selective agonist of CB2 and activator of CB1 that is involved in promotion of neuronal recovery and survival. The role of combined application of JWH-015 with AM251 in the rat model of GCI has been surveyed in this study. Male Wistar rats underwent 20 min of ischemia followed by reperfusion. Then, 1 mg/kg JWH-015 and 2 mg/kg AM251 were administered through caudal vein. The groups were control, sham, ischemia, vehicle, AM251, JWH-015 and AM251 + JWH-015. Animals were sacrificed at 14 days after reperfusion. The AM251 + JWH-015 group showed a significant increase in the protein expressions of AKT1, Bad 14-3-3, Bcl-2 and Bcl-XL, but it showed a considerable decrease in the protein expressions of Bad and JNK1/2 (p ≤ 0.05 vs. AM251, and JWH-015 groups). The AM251 + JWH-015 group had a significant higher number of alive cells and lower number of TUNEL-positive cells in the CA1 hippocampal area, and it also had a considerable improvement of spatial memory (p ≤ 0.05 vs. AM251, and JWH-015 groups). The results of this study showed that combined application of AM251 and JWH-015 could be neuroprotective against detrimental effects of ischemia probably via suppression of neuronal apoptosis and maintenance of their survival.