Various organic solvents like methanol, chloroform, alcohol, dimethyl formamide; acetonitrile, hexane, acetone and carbon tetrachloride have been employed for solubilization of poorly water-soluble drugs for spectrophotometric estimations. Drawbacks of organic solvents include high cost, toxicity and error in analysis due to volatility. Attempting to minimize these drawbacks, three new, simple, accurate, environmental friendly, cost effective, safe, sensitive spectrophotometric methods have been developed for simultaneous estimation ofloxacin and ornidazole in tablet dosage form by using aqueous solution of 2.0 M sodium benzoate solution, as a hydrotropic agent. Aqueous solubility of these model drugs was enhanced to a great extent 5 and 11 fold for ofloxacin and ornidazole in 2.0 M sodium benzoate solution respectively. Sodium benzoate solution and additives of tablet did not interfere in analysis, as sodium benzoate did not show any absorbance above 300 nm. Quantitative estimation of these drugs in tablet dosage form was carried out by method-I, first order derivative spectrophotometric, method-II area under curve and method-III multi-component methods of spectrophotometric analysis. Both drugs obeyed Beer’s law in the concentration ranges employed for theses methods. Results of analysis were tested and validated for various parameters according to ICH guidelines; hence the proposed methods can be adopted for the routine analysis of ofloxacin and ornidazole in tablet dosage form.