In this study, chemometric approaches using UV spectrophotometry method developed models for simultaneous determination of valsartan (VAL) and amlodipine (AMP) in drug samples. It was used to calculate calibration mixtures between 232 and 254 nm wavelengths at 2 nm intervals for Val and AML spectra at various concentrations. For chemometric analysis of data, the least squares calibration method and basic component regression were used, and the parameters of chemometric procedures were optimized. The analytical performances of this chemometric method were compared by characterizing the sum of residual error squares (PRESS), estimated standard error (SEP), and recoveries (%). A number of synthetic mixtures containing different concentrations of VAL and AML were studied to control the predictive ability of Applied chemometric methods. This method was successfully applied to the actual samples, not affected by the auxiliaries as indicated in the recovery study results. The results obtained in this review encourage these chemometric methods to implement these strategies for standard research and quality control of the two active ingredients.