Background: Stroke is among the leading causes of death worldwide, but current treatment options for cerebral ischemia are limited. Chrysoeriol is a natural isolated agent with bioactive pharmacological properties. Materials and Methods: Sprague–Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) surgery and chrysoeriol was administrated for the subsequent 3 days. Neurological deficit scores, apoptosis, oxidant stress, and inflammatory cytokines were then measured and the effects on the Wnt/β-catenin pathway were evaluated. Results: Behavioral tests revealed that chrysoeriol promoted recovery from neurological deficits in rats. Hematoxylin and eosin staining demonstrated that chrysoeriol alleviated neurological damage. Triphenyl tetrazolium chloride staining demonstrated that chrysoeriol reduced the area of ischemia. An enzyme-linked immune sorbent assay (ELISA) demonstrated that chrysoeriol inhibited excessive pro-inflammatory cytokine production (tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) and regulated oxidative stress (malondialdehyde, superoxide dismutase, and glutathione). Caspase-3 immunofluorescence and a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay showed that chrysoeriol reduced neuronal apoptosis. The ELISA assay and Nissl staining showed that chrysoeriol promoted neuronal survival and growth. Western blotting and an immunofluorescence assay demonstrated that the Wnt/β-catenin signaling pathway plays a crucial role in the neuronal effects of chrysoeriol. The Wnt inhibitor, Dickkopf-related protein-1, validated the role of the Wnt/β-catenin signaling pathway in the neuroprotective effects of chrysoeriol. Conclusion: Chrysoeriol exerts neuroprotective effects in a rat model of MCAO. These effects are mediated by the Wnt/β-catenin signaling pathway.