Accurate, precise, rapid and economical first order derivative spectroscopic method was developed and validated for the estimation of Cefixime and levofloxacin in tablet. The wavelengths selected for quantitation were 289.45 nm for levofloxacin (zero cross for cefixime) and 317.0 nm for cefixime (zero cross for levofloxacin). Linearity for detector response was observed in the concentration range of 2-12 μg/ml for both Cefixime and Levofloxacin using methanol as a solvent with correlation coefficient 0.991 and 0.993 respectively. The proposed method was successfully applied for the simultaneous estimation of both drugs in tablet.