Glimepiride, an antidiabetic drug was classified as Class II drug in Biopharmaceutical Classification System (BCS) due to its low solubility (< 0.004 mg/mL) and high permeability. The aim of this work was to investigate the use of palm-oil polyesteramide (POPEA) and stearic acid-based polyesteramide (SAPEA) as carrier in GMP solid dispersion (SD) to increase dissolution rate and solubility. Glimepiride SDs were prepared by solvent evaporation technique, using POPEA and SAPEA as a polymer carrier. The SDs were characterised for drug content, solubility, dissolution and physico-chemical characteristics by DSC, FTIR and SEM. All SDs demonstrated faster dissolution rate and solubility as compared to the pure glimepiride. The optimized SD B9 showed 4-fold improvement of drug release (77.42 ± 0.79%) against pure glimepiride (18.33 ± 3.10%) at 2 h of dissolution. DSC endothermic peak for glimepiride in optimized SD B9 (90% glimepiride, 10% SAPEA) was broadened and shifted to lower temperature (198°C). FTIR spectroscopy confirmed no chemical changes in glimepiride SD. SEM images showed the irregular, less crystalline and smaller size of SD which improved the solubility and dissolution rate due to the transformation of glimepiride crystalline structure to amorphous form. POPEA and SAPEA as a drug carrier demonstrated good characteristic in improving the aqueous solubility and dissolution rate of glimepiride in SD.