ABSTRACT: Glipizide (GLZ) is an oral hypoglycemic agent, which is a weakly aqueous soluble drug. The solubility values of GLZ in various neat solvents are scarce in the literature. Hence, the solubility of GLZ in 12 different neat solvents, namely, "water, methanol, ethanol, isopropanol (IPA), 1-butanol, 2-butanol, ethylene glycol (EG), propylene glycol (PG), poly(ethylene glycol)-400 (PEG-400), ethyl acetate (EA), dimethyl sulfoxide (DMSO), and Transcutol-HP (THP)", at "T = 298.2-318.2 K" and "p = 0.1 MPa" was measured. The recorded solubilities of GLZ were correlated by "van't Hoff and Apelblat models" using root-mean-square deviation (RMSD). The overall RMSD was obtained as 1.21 and 1.40% for "Apelblat and van't Hoff models", respectively. Different solubility parameters of all studied materials including drug and solvent were calculated to find the best solvent for GLZ. The solubilities of GLZ (expressed in mole fraction) have been found highest in DMSO (2.81 × 10-2), followed by THP, EA, 2-butanol, 1-butanol, IPA, PEG-400, ethanol, PG, methanol, EG, and water (1.98 × 10-4) at "T = 318.2 K". All investigated solubility parameters of GLZ were recorded very close to the DMSO. "Apparent thermodynamic analysis" showed an "endothermic and entropy-driven dissolution" of GLZ in the 12 different neat solvents. The highest molecular interactions were recorded in GLZ-DMSO compared to other combinations. Overall, DMSO has been considered as the best solvent for the solubilization of GLZ.