The design and fabrication of therapeutic bone scaffolds that combine bioactive materials with osteoinductive drugs is a promising strategy for bone regeneration. Herein, we firstly developed icariin loaded-hollow bioglass/chitosan (ICA/HBG/CS) therapeutic scaffolds to treat critical-sized bone defects. The HBG/CS hybrid scaffolds possessed three-dimensional (3D) interconnected macropores with sizes of approximately 200 mu m, which not only promoted the adhesion and spreading of stem cells, but also accelerated the in-growth of bone tissues. The HBG microspheres with hollow core and mesoporous shell were uniformly distributed on the macropore walls. The ICA drugs could be controllably released from the therapeutic scaffolds because of the hierarchically porous structures and hydrogen-bonding interactions. The as-released ICA drugs from the scaffolds remarkably upregulated the expression levels of osteogenic-related genes (COL1 and RUNX2) and osteogenic-related proteins (ALP and p-Smad1/5). The micro-CT images, Masson's trichrome staining and double fluorochrome labelling results revealed that the ICA/HBG/CS therapeutic scaffolds remarkably accelerated the formation of new bone tissues compared to the scaffolds without ICA drugs. Hence, the ICA/HBG/CS therapeutic scaffolds including bioactive materials and osteogenic drugs can serve as a kind of novel and promising bone materials for enhanced osteogenic differentiation and new bone regeneration.