The objective of this study was to evaluate the biological activity enhancement of a novel glycidyl methacrylated dextran (Dex-GMA)/gelatin hybrid hydrogel containing microspheres loaded with bone morphogenetic proteins (BMP) as periodontal cell/tissue scaffold. Larger number of human periodontal ligament cells (PDLCs) attached was observed in scaffolds containing microspheres loaded with BMP when compared to those without microspheres. When osteogenic differentiation of PDLCs in such scaffolds was evaluated, the alkaline phosphatase (ALP) activity, osteocalcin content, and calcium deposition became maximum for the scaffold containing microspheres loaded with BMP, as compared with those without microspheres but adsorbed with the same amount of BMP aqueous solution, although both values were significantly higher than those in BMP-free scaffold. In addition, the osteoinduction activity was also studied following the implantation of these scaffolds into the periodontal defects of dogs in terms of histological examinations, significantly more new bone formation and periodontal ligaments regeneration were observed throughout scaffold containing microspheres. We conclude that the attachment, proliferation, and osteogenic differentiation of PDLCs can be enhanced by Dex-GMA/gelatin hydrogel scaffold containing microspheres loaded with BMP, and such scaffold is promising to enhance periodontal tissue regeneration in periodontal therapy.