Remote ischemic postconditioning (RIPostC) has been reported to have a brain-protection effect on ischemic stroke. In the previous studies, we found that the circRNA_0002286/ miR-124-3p/very long-chain acyl-CoA dehydrogenase (VLCAD) pathway may play a regulatory role in ischemic stroke injury. However, the regulatory mechanism of the pathway remains unknown. In this study, different reperfusion times were respectively set to screen the optimal treatment time of oxygen-glucose deprivation/reoxygenation (OGD/R), then primary neurons and PC12 cells were induced by OGD/R. The RIPostC rat model was established by repeatedly clamping the femoral artery after transient middle cerebral artery occlusion. Reverse transcription real-time polymerase chain reaction was performed to detect the expression of circRNA_0002286, miR-124-3p, and VLCAD mRNA. Western blot was used to detect VLCAD protein. The fluorescence intensity of NeuN was detected using immunofluorescence staining. Dihydroethidium staining was performed to observe cell hypoxia. The targeting relationship among miR-124-3p, circRNA_0002286, and VLCAD was verified by dual-luciferase reporter assay. Fluorescence in situ hybridization assay was used to detect the localization of circRNA_0002286 and miR-124-3p in PC12 cells. Cell viability was measured using cell counting kit-8. Cell apoptosis was evaluated using Annexin V/FITC/PI double staining. 2,3,5-triphenyl tetrazolium chloride, hematoxylin-eosin, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were used to observe the pathological damage of brain tissue in rats. Results found that circRNA_0002286 and VLCAD mRNA decreased in OGR/R-induced neurons, PC12 cells, and RIPostC rats. Knockdown of circRNA_0002286, overexpression of miR-124-3p, or knockdown of VLCAD inhibited the proliferation and induced apoptosis of PC12 cells, promoted brain damage in rats. Overexpression of circRNA_0002286, miR-124-3p inhibition, or overexpression of VLCAS promoted brain protection of RIPostC rats. Mechanistically, overexpression of circRNA_0002286 promoted VLCAD level through sponging miR-124-3p and enhanced the neuroprotective effect of RIPostC. In conclusion, circRNA_0002286/miR-124-3p/VLCAD regulatory network may be a prospective therapeutic target for ischemic stroke.