Two methods are described for the simultaneous determination of mebeverine hydrochloride (MB) and sulpiride (SU) in their combinations. The first method depends on the first derivative of the ratio spectra by measurement of the amplitudes at 263.7 and 234.9 nm for MB and SU, respectively. The linear ranges and detection limits are 4.0 - 40.0 and 0.72 µg/ml for MB and 1.0 - 10.0 and 0.34 µg/ml for SU. In the second case, a chemometric (classical least squares) method was developed. The concentration data matrices were obtained by using different concentrations of pure drugs in 0.1 M HCl. The absorbance data matrix corresponding to each concentration data matrix was obtained by the measurements of absorbances in the range 200 - 300 nm in their zero order spectra; then calibration was obtained by using the absorbance data matrix and the concentration data matrix for the prediction of the unknown concentrations of MB and SU in their mixture. The numerical values were calculated by using Matlab R12 version 6.0 and Origin 5.0 software. The procedures do not require any separation steps. These two methods were successfully applied for assaying the pharmaceutical formulation, of Colona tablets.