Microsphere integrated gelatin-siloxane hybrid scaffolds were successfully synthesized by using a combined sol-gel processing, post-gelation soaking and freeze-drying process. A bone-like apatite layer was able to form in the Ca2+-containing porous hybrids upon soaking in a simulated body fluid (SBF) up to 1 day. The rate of gentamicin sulfate (GS) release from the GS-loaded gelatin-siloxane hybrid microsphere became constant after a 4 h burst. The antibacterial activity was assessed by the agar diffusion test (ADT) and the bactericidal effect test. It is evident that the as-synthesized porous scaffolds have excellent bioactivity and antibacterial activity, and may be favorable in bone tissue engineering.