The main aim of the present study was to design and assess the twice-daily sustained-release matrix tablets of Nitazoxanide using different concentrations of hydrophilic polymers. Wet granulation method was used to prepare Nitazoxanide sustained-release tablets by using HPMC (Hydroxypropyl Methylcellulose) K4M, HPMC K15M. The prepared tablets were assessed for release during 12 h by using USP type- II dissolution apparatus. Physical properties of Nitazoxanide tablets were studied. The in vitro release studies of sustained-release tablets were plotted in the form of graphs. The in vitro release study showed that F12 was the best formulation, extending the drug release up to 12 h, and it exhibited suitable drug release in the initial hours and the total release pattern was similar to the theoretical release profile. The drug release optimized formulation (F12) followed first-order kinetics. In vitro drug release of Nitazoxanide sustained-release tablets indicated that Nitazoxanide sustained-release tablets could therapeutically perform better than conventional tablets with better patient compliance and improved efficacy.