Bone and joint infections pose a serious challenge in the orthopedic medical condition which presents a major health care problem and economic burden to the patients. The current treatment strategies adopted have a very limited successful outcome in majority of the cases and need serious reconsiderations in terms of management, diagnosis and effective treatment approach. Herein, we have developed a composite cryogel scaffold from nanohydroxyapatite and collagen mimicking natural bone composition for the local delivery of antibiotic to treat osteomyelitis. The biomimetic and biodegradable antibiotic-loaded composite scaffold was found to be biocompatible with potent osteogenic capacity and anti-infective characteristics under in vitro conditions. Moreover, the anti-infective potency of the antibiotic-loaded composite cryogel was also evaluated in rat osteomyelitis model to cure the infection and promote bone healing. It was observed that anti-infective collagen-nanohydroxyapatite composite cryogel when loaded with bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA) could completely eradicate the infection in rat femoral condyle and simultaneously, accelerate bone healing at the dead space created during surgical procedures. The approach developed in this study is the development of biomimetic and bioactive composite carrier of antibiotics for the treatment of bone infection. The findings of this study insinuate that this antibiotic-loaded composite cryogel scaffold could potentially be used as an anti-infective biomaterial for the treatment of bone infections which will simultaneosuly promote bone healing at the dead space created during surgical procedures.