Solution thermodynamics and solubility of glibenclamide (GBN) in binary co-solvent mixtures of Transcutol + water at temperature range of 298.15–333.15 K were investigated in present study. The modified Apelblat model was used to predict the solubility of GBN in co-solvent mixtures at various temperatures. The highest and lowest solubility of GBN were observed in pure Transcutol and pure water, respectively. Moreover, all co-solvent mixtures had highest solubility at 333.15 K. The experimental solubility data of GBN was correlated well with the modified Apelblat model at each temperature studied with relative absolute deviation in the range of 0.008–5.903 %. The correlation coefficients in co-solvent mixtures were observed in the range of 0.995–0.999 which indicated good fitting of experimental data with calculated one. The enthalpies and entropies for GBN dissolution were observed in the range of 2.012–38.215 kJ mol−1 and 6.748–114.709 J mol−1 K−1, respectively indicating its dissolution is endothermic and an entropy-driven process. These results indicated that Transcutol can be used as a co-solvent in preformulation studies and formulation development of GBN.