The stability of human serum albumin (HSA) is studied before and after incubation with glucose utilizing differential scanning Calorimetry (DSC) and circular dichroism (CD) techniques. The incubation of HSA with glucose results in its nonenzymatic glycosylation that is glycosylated HSA (GHSA) formed in glucose concentrations (8.25, 16.5 and 27.5 mM) in a temperature dependent manner. The DSC profiles of GHSA samples, which indicate changes in heat capacity C-p and C-p(excess) versus temperature, were obtained and the thermal denaturation reversibility of each sample was assessed up to 80 degreesC. The melting point (T-m), the change of enthalpy, and the heat capacity for GHSA at different glucose concentrations were obtained. The results showed that glucose at lower concentrations induces the destabilization of HSA while at higher concentrations induces its stabilization. In addition, considerable conformational changes in HSA were observed after incubation with glucose. This was demonstrated through deconvolution of DSC profiles that imply the formation of new energetic domains, which were further confirmed by the presence of alpha-helices in the CD spectrum.