The aim of this research study is the preparation and characterization of graded glass-ceramic scaffolds that are able to mimic the structure of the natural bone tissue, formed by cortical and cancellous bone. The material chosen for the scaffolds preparation is a glass belonging to the system SiO( 2)-P(2)O(5)-CaO-MgO-Na( 2)O-K(2)O (CEL2). The glass was synthesized by a conventional melting-quenching route, ground, and sieved to obtain powders of specific size. The scaffolds were fabricated using different methods: polyethylene burn-off, sponge replication, a glazing-like technique, and combinations of these methods. The scaffolds were characterized through morphological observations, density measurements, volumetric shrinkage, mechanical tests, and in vitro bioactivity tests. The features of the scaffolds prepared using the different methods were compared in terms of morphological structure, pores content, and mechanical strength. The proposed scaffolds effectively mimic the cancellous/cortical bone system in terms of structure, porosity, and mechanical strength, and they exhibit a highly bioactive behavior. Therefore, these graded grafts have a great potential for biomedical applications and can be successfully proposed for the substitution of load-bearing bone portions.