Simultaneous spectrophotometric determination of diacerein and aceclofenac was performed by partial least-squares (PLS) and principal component regression (PCR) methods do not require any priori graphical treatment of the overlapping spectra of two drugs in the mixture. The absorbance values in the UV-Vis spectra were measured for the 67 wavelength points (from 234-300) in the spectral region 200–400 nm considering the intervals of 1 nm. The calibration range was found to be 1-5 μg/ml for diacerein, 2-10 μg/ml for aceclofenac with a correlation coefficient of 0.9998(PLS), 0.9995(PCR) for diacerein and 0.9999 (PLS), 0.9997 (PCR) for aceclofenac. The validation of the multivariate methods was realized by analyzing the synthetic mixtures of diacerein and aceclofenac. The numerical calculations were performed with the ‘Unscrambler 10.1 X’ software. The chemometrics analysis methods were satisfactorily applied to the simultaneous determination of diacerein and aceclofenac in the pharmaceutical formulation.