This article discloses the development of an effective and versatile technology to prepare a novel antibiotics-loaded biodegradable composite bone cement to treat methicillin-resistant Staphylococcal (MRSA) osteomyelitis and reports its detail in vitro characterization, drug loading efficiency, physico-mechanical properties, drug elution in simulated body fluid (SBF) and human plasma, merits and demerits over poly-methyl methacrylate (PMMA) cement. Chronic osteomyelitis in rabbit tibia (42) was induced by MRSA and composite cement was implanted to evaluate its safety and efficacy over PMMA cement and parenteral treated animals with histopathology, radiographs, bone/plasma drugs concentration, and SEM for 90 days. The composite cement showed higher setting time, degradability, pH rise, injectability, in vitro drug elution but lesser mechanical strength than PMMA cement. Antibiotics release from cement beads was faster in SBF than plasma. Further, in vivo antibiotics elution from composite (42 days) showed effective concentration against MRSA without eliciting drug-toxicity. Platelets activation by composite was an extraordinary feature. The in vivo studies also proved the superiority of composite cement than other treatment methods in terms of faster infection control and osteosynthesis. Based particularly on drug elution and in vivo results, this newly developed cement can successfully be used in clinical cases of chronic osteomyelitis.