The biodegradability and biocompatibility properties of poly(ε-caprolactone) place it as a valuable raw material, particularly for controlled drug delivery and tissue engineering applications. However, the usefulness of such materials is limited by their low hydrophylicity and slow biodegradation rate [1, 2]. As copolymerization with insertion of more hydrophilic structural units can improve polycaprolactone (PCL) properties and functionalities, copolymerization of εcaprolactone (ECL) with gluconolactone (GL) was optimized by a 3-factorial-3 level experimental design, using the Box-Behnken method. The selected independent variables were the temperature, the enzyme/substrate ratio and the molar ratio of monomers, while the copolymer polymerization degree and the weight average molecular mass (determined from the MALDI-TOF MS spectra) were considered as response variables. The results indicate that temperature has the most significant effect and is directly correlated with the formation of linear copolymers. The overall effect of the other variables was also significant. The thermal stability of the ECL-GL copolymers, compared to synthesized homopolymer PCL and δ-gluconolactone has been assessed by thermogravimetric analysis (TGA), while differential scanning calorimetry (DSC), was used to measure the heat capacity as a function of temperature. The thermoanalytical curves indicate a decrease in the thermal stability of the copolymer, compared to the homopolymer. Mass loss begins around the temperature of 100 °C. Compared to the homopolymer, copolymer degradation takes place in two steps, as confirmed by the inflections at 270.9 ºC and 430.7 ºC, respectively. The DSC curves present two endothermic peaks at 50 ºC and 153 ºC, probably due to internal transitions that may occur. The thermoanalytical techniques can consistently improve the utilization efficiency of polymer-based formulations in pharmaceutical and medical applications.