Mandibular bone regeneration is stepped up by human recombinant bone morphogenetic protein 2 (BMP-2) whose application is also related to limited cementum and periodontal ligament regeneration, local root resorption, and ankylosis. The alveolar bone grafting without traditional autologous bone grafts remains a challenge for plastic surgeons. Bilateral mandibular alveolar and periodontal defects were created over the premolar areas in 9 mature male beagles. The defects were randomly assigned for either the adenovirus BMP-2 (advBMP-2) group with BMP-2-expressing mesenchymal stem cells (MSCs) or the control with MSCs alone. The regenerated periodontal attachment apparatus was evaluated histologically, and the whole regenerated bone volume was scrutinized from three-dimensional computed tomography analysis. Periodontal apparatus regeneration was significantly better in the advBMP-2 group. New cementum and Sharpey fibers were observed on the denuded root surfaces in the advBMP-2 group, whereas incomplete healing with localized root surface resorption was noted in the control group. Eight weeks after implantation, the advBMP-2 group showed significant increase in bone regeneration than the control one. Thus, the use of ex vivo BMP-2-engineered autologous MSCs boosted bone and periodontal apparatus regeneration in mandibular periodontal defects. This de novo approach might be suitable for clinical mandibular bone repair and periodontal apparatus repair.