Chemometrics is the subdivision of analytical chemistry that uses computational methods for qualitative or quantitative analysis of typically multivariate measurement data. In this study, chemometric assisted UV spectrophotometric method was developed and validated for estimation of Ofloxacin and Cefpodoxime proxetil. Chemometric methods used were principle components regression (PCR) and partial leastsquares regression (PLS) for data analysis. Spectra of Ofloxacin and Cefpodoxime proxetil were recorded between wavelengths of 220 to 320nm with wavelength interval of 0.5 nm in linearity range of 5.0-30.0 µg/ml for both the drugs. The methods were validated as per International Conference on Harmonization Q2 (R1) (ICH) guidelines. These methods were successfully applied for determination of drugs in pharmaceutical formulation (tablet) with no interference of the excipients as indicated by the recovery study results. The proposed methods are simple, rapid and can be easily used as an alternative analysis tool in the quality control as well as in process control of drugs and formulation