Two distinct spectrophotometric methods are provided in this paper for simultaneous measurement of Amlodipine Besylate and Candesartan Cilexetil in bulk and formulation. Two chemometric approaches were used to quantitatively resolve overlapping spectra, Inverse least squares (ILS) and the Classical least square method (CLS). Calibration curves were plotted using the absorbance and concentration of mixed solutions of two drugs. The drugs; Amlodipine Besylate and Candesartan Cilexetil were found to be linear in the 5–15 and 8–24 µg/ml range. The data matrix of absorbance was generated by determining absorbance in a wavelength range from 300 to 360 nm. A calibration set composition of concentration of a different mixture of Amlodipine Besylate and Candesartan Cilexetil was assembled statistically to optimize the particulate content from the spectra in a way to get minimal errors in multivariate calibrations. The algorithms of CLS and ILS were applied to spectra of the mixed solution of two drugs in a calibration set and a suitable matrix was acquired. The model from CLS and ILS was selected by studying the values of RMSEP. Then this algorithm was applied to the prediction set of different mixtures of two drugs and marketed formulation. The results of the recovery study of the marketed formulation were determined with great sensitivity in terms of limit of detection and limit of quantification. These CLS and ILS methods are validated and employed for the quantification of drugs in mixtures and formulation.