This presented work is based on application of two multivariate calibration methods for simultaneous UV-Vis spectrophotometric determination of active substances in combined pharmaceutical formulation composed of Ciprofloxacin (CPX) and Ornidazole (ONZ). The methods used were Principal Component Regression (PCR) and Partial Least Square (PLS). The Spectra of both CPX and ONZ were recorded at concentrations within their linear ranges 2.0-12.0 µg/ml. 27 set of mixtures were used for calibration and 9 set of mixtures were used for validation in the wavelength range of 267 to 330 nm with the wavelengths intervals λ= 0.5 nm in methanol. International Conference on Harmonization Q2 (R1) (ICH) guidelines were followed to validate the methods. Recovery study results indicate no interference of the excipients, thus methods were successfully applied for determination of drugs in pharmaceutical formulation. The methods can be used as alternative analytical tool in the quality control of these drugs.