A simple, sensitive, rapid, accurate and precise method for simultaneous determination of Nitazoxanide and Ofloxacin in combined tablet dosage form has been developed. The method is based on ratio spectra derivative spectrophotometry. The amplitudes 269 nm and 236.5 nm in first derivative of the ratio spectra were selected to determine Nitazoxanide and Ofloxacin respectively in combined formulation. The developed method was showing linearity in concentration range of 5-30 µg/ml for Nitazoxanide and 2-12 µg/ml for Ofloxacin with correlation coefficient (R²) 0.999 and 0.996; respectively. The percent assay was found to be 99.12 % and 100.69 % for Nitazoxanide and Ofloxacin, respectively. The method showed good linearity, precision and reproducibility. Results of analysis were validated statistically and by recovery studies.