Bone morphogenetic protein-2(BMP-2) was widely used in orthopedics and dental implant surgery but there are a variety of side effects including unwished bone formation, cancerous signaling process. To solve these problems, novel synthetic peptide (osteogenic peptide-5, OP-5) derived from BMP-2 was developed for clinical use. The OP-5 influence was evaluated by in vitro and in vivo assay compared with BMP-2. To optimize the osteogenic effects, it was conjugated onto electrospun fibers fabricated from poly(L-lactide). The peptide tightly attached to nanofibers and it was maintained at least 28 days, in vivo mouse calvarial defect model showed that OP-5 conjugated nanofibers could increase the bone regeneration and mechanical property similar to BMP-2 coated PLLA. Our results suggested that OP-5 can be used as new therapeutic agents for bone regeneration and OP-5 conjugated nanofibers might be a feasible method as guided bone regeneration for a dental and orthopeadic treatment.