Poly(2-ethyl-2-oxazoline) (PEOX), a biocompatible polymer considered as pseudo polypeptide, was introduced as a potential alternative to the commonly used polymer, poly(vinylpyrrolidone) (PVP) for the preparation of solid dispersion with a poorly soluble drug. Glipizide (GPZ), a BCS class II model drug, was selected for solubility and dissolution rate study. GPZ-polymer solid dispersions and physical mixtures were characterized and investigated by X-Ray diffractometry, differential scanning calorimetry, scanning electron microscopy, and Fourier transform infrared spectroscopy. The impact of polymers on crystal nucleation kinetics was studied and PEOX exhibited strong inhibitory effect compared to PVP. Solubility and dissolution behavior of the prepared solid dispersions and their physical blends were in-vitro examined and evaluated. A significant enhancement in glipizide solubility was obtained with PEOX compared to the pure drug and solid dispersion with PVP. A big improvement in the intrinsic dissolution rate (45 times) and dissolved amount of glipizide (58 times) was achieved with PEOX in FaSSIF (fasted state simulated intestinal fluid), against comparable enhancement observed with PEOX and PVP in phosphate buffer at pH 6.8. Lower molecular weight of PEOX-5K (5,000 g/mol) was found to be superior to higher molecular weight PEOX-50K (50,000 g/mol) in the improvement of dissolution behavior. The findings of this study with glipizide as a model drug introduce lower molecular weight PEOX as a promising polymeric carrier toward better oral bioavailability of poorly soluble drugs.