Implantation of a scaffold into the body in a safe and convenient manner remains a challenge in the repair of patient bone defect. In the present study, a strategy for fabrication of the redox-sensitive nanofibers with a core-shell structure that can deliver the growth factors in a tunable manner is presented. Poly(ethylene oxide) (PEO) and bone morphogenetic protein 2 (BMP-2) forms the inner core region, and a mixture of poly(epsilon-caprolactone) (PCL) and redox-responsive c-6A PEG-PCL nanogel with -S-S- bond forms the outer shell. The redox-sensitive shell of the nanofibers can respond the change of the GSH (glutathione) concentration and thus regulate the BMP-2 release behavior in vitro and in vivo. In vitro cytotoxicity results indicated that the redox-sensitive nanofiber had good osteoinduction. The in vivo results demonstrated that the nanofibers exhibited a capacity of prompting new bone generation in the bone defect. Therefore, the redox-responsive nanofiber in the present study may be of great potential for application in bone reconstruction.