Nitazoxanide is a broad-spectrum antiparasitic and antiviral agent widely used in the treatment of diarrhoea caused by protozoa such as Giardia lamblia and Cryptosporidium parvum. Despite its clinical effectiveness, Nitazoxanide suffers from certain pharmacokinetic limitations, including poor aqueous solubility, low oral bioavailability, and a short plasma half-life. To address these challenges, a gastro retentive drug delivery system in the form of floating microspheres was developed to enhance the drug’s bioavailability and prolong its residence time in the stomach. The floating microspheres were prepared using the solvent evaporation method, in which HPMC and Ethyl cellulose were used as a polymer, DCM and ethanol used as a solvent, Tween 80 is used as a surfactant. Six formulation batches were fabricated and evaluated for parameters such as micromeritic properties, particle size, Percentage entrapment efficiency, percentage yield, Percentage in-vitro buoyancy behavior, surface morphology, zeta potential and in vitro drug release profile. The physicochemical properties of microsphere strongly affected by the presence of drug/polymer ratios. Among all formulations, batch F5 shows highest % entrapment efficiency (78.1%), % yield (84.1%), In-vitro buoyancy (87.9%), Zeta potential of -20.3mV and moderate particle size. The drug is released upto 12 hrs. and 76.02% of drug has been released from the formulation representing the controlled release nature.