The possibility of combining the advantages of bioresorbable polymers blending and the modification of blend matrix with bioactive ceramic fillers was presented for the first time in order to obtain composite materials for biomedical applications. Two kinds of sol-gel-derived bioactive glasses: S2-high silica and A2-high lime content were combined with PCL/PLGA blend at different volume ratio, that is, 25/75, 50/50, and 75/25. Materials were fabricated in the form of thin films using a solvent casting method. The influence of these variables on surface properties (morphology, roughness, wettability), their mechanical performance, in vitro bioactivity and Saos-2 osteoblast-like cell response (cell viability, alkaline phosphatase activity), were successfully investigated. Due to the specificity of fabrication route, studies were conducted to examine the opposite surfaces of the films, that is, Petri dish glass- or air-exposed during casting. It was demonstrated that the PCL/PLGA ratio of blend matrix, as well as chemical composition of gel-derived bioactive glass particles, are two-key factors that allow altering the surface and mechanical properties of the materials in a wide range. This, in turn, modulates significantly the bioactivity of materials and the response of osteoblast-like cells. Our findings indicate the new possibilities of designing biodegradable and highly bioactive composite materials with potential osteogenic properties.