<p>Alveolar bone defects following tooth extraction in severe periodontitis pose significant clinical challenges. This study evaluates the synergistic osteogenic effect of Er, Cr: YSGG laser combined with guided bone regeneration (GBR) in rat extraction sockets and explores the underlying Wnt/β-catenin pathway mechanism. Fifty Sprague-Dawley rats were randomized into five groups (<i>n</i> = 10/group): Control (extraction only), Laser (Er, Cr: YSGG laser irradiation only), GBR (Bio-Oss bone graft + barrier membrane), Laser+Bone Graft (laser irradiation + Bio-Oss without membrane), and Laser + GBR (laser irradiation + Bio-Oss + barrier membrane). At 4 and 8 weeks post-operation, CBCT quantified bone volume fraction (BV/TV) and bone mineral density (BMD). Histological staining was used to evaluate new bone formation. ELISA and qPCR analyzed osteogenic markers (β-catenin, Runx2, BMP-2) and the Wnt pathway inhibitor (DKK-1). MSD assays quantified β-catenin nuclear translocation and the p-GSK-3β/GSK-3β ratio to assess pathway activation. The Laser + GBR group demonstrated the highest BV/TV and BMD at 8 weeks, with complete scaffold degradation, dense trabeculae, and minimal inflammatory infiltration on histology. ELISA and qPCR confirmed the highest expression of β-catenin, Runx2, and BMP-2 alongside the lowest DKK-1 levels in this group at both time points. MSD detection revealed the highest β-catenin nuclear translocation rate and the lowest p-GSK-3β/GSK-3β ratio, indicating robust Wnt/β-catenin pathway activation. Er, Cr: YSGG laser synergizes with GBR to enhance alveolar bone regeneration, likely by suppressing DKK-1, inhibiting GSK-3β activity, and promoting β-catenin nuclear translocation, thereby activating the Wnt/β-catenin pathway and upregulating downstream osteogenic genes. This combination represents a promising strategy for post-extraction bone defect repair.</p><p>Clinical Trial Number: Not applicable.</p>