The purpose of present research work was to formulate the Glipizide (sulphonyl urea, antidiabetic agent) in sustained release tablet dosage form for the management of type II Diabetes Mellitus. Glipizide is having short biological half-life (2-4 h) & classified as class II in the biopharmaceutical classification system (BCS) thus, Sustained release delivery system is chosen to provide a uniform concentration of the Glipizide at the absorption site. The matrix tablets were prepared by direct compression method. The drug excipients compatibility was evaluated by Fourier transform infrared (FTIR) spectroscopy studies it confirms that there is no interaction between the drug and polymers used. The formulation batches of Glipizide matrix tablets were designed by employing three different hydrophilic polymers, HPMC K4M & HPMC K100M as synthetic polymer and Karaya Gum as natural polymer. All three polymers are used alone. The combination of Karaya Gum with synthetic polymers at various concentrations was taken to the see the combination effect. The effectiveness of the synthetic (HPMC K4M & HPMC K100M) and natural Polymer (Karaya Gum) was compared, also their combination effect on release profile of Glipizide was studied. The pre-compression study was performed and the results were reported. In pre-compression study the angle of repose, bulk density, tapped density, Hausner’s ratio and Carr’s index was calculated and results shown the good compliance as per IP standards. The tablets parameters were evaluated by testing weight variation thickness, hardness, friability test etc. From the dissolution Profile of formulation batches F1 to F11 the effect of polymer concentration on dissolution profile of tablet can be seen clearly. As concentration of polymer increases the drug release decreases.