In this contribution, a novel smart drug delivery system (DDS) consisting of hydroxyl-functionalized glycerol poly(epsilon-caprolactone) (PGCL)-based microspheres and poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was developed for prolonged and sustained controlled drug release. Various amounts PGCL-based microspheres were incorporated physically into temperature sensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel to form the novel DDSs. Resulting DDSs were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and compression modulus measurements to investigate the morphological, thermal, and mechanical properties. The temperature dependence of swelling ratio and response kinetics upon heating or cooling were also investigated to understand the smart properties, i.e., temperature sensitive properties of these DDSs. Finally, ovalbumin (OVA), used as the model drug, was loaded into PGCL-based microspheres to examine and compare the effects of controlled release at different temperature (22 and 37 degrees C) of these novel smart DDSs.