Biodegradable polymers have been used with various systems for tissue engineering. Among them, poly(lactic-co-glycolic) acid (PLGA) has been widely used as a biomaterial for bone regeneration because of its great biocompatibility and biodegradability properties. However, there remain substantial cruxes that the by-products of PLGA result in an acidic environment at the implanting site, and the polymer has a weak mechanical property. In our previous study, magnesium hydroxide (MH) and bone extracellular matrix are combined with a PLGA scaffold (PME) to improve anti-inflammation and mechanical properties and osteoconductivity. In the present study, the development of a bioactive nanocomplex (NC) formed along with polydeoxyribonucleotide and bone morphogenetic protein 2 (BMP2) provides synergistic abilities in angiogenesis and bone regeneration. This PME hybrid scaffold immobilized with NC (PME/NC) achieves outstanding performance in anti-inflammation, angiogenesis, and osteogenesis. Such an advanced PME/NC scaffold suggests an integrated bone graft substitute for bone regeneration.