In this paper, hydrochlorothiazide (HCT) and losartan potassium (LSP) in tablets are simultaneously determined with UV-Vis spectrophotometry and chemometrics without separation. The spectra of standard and sample solutions were recorded in the wavelength from 220 to 300 nm at 1.0 nm intervals. The concentrations of HCT and LSP in the sample solutions were computed with the Kalman filter algorithm written on the Microsoft Excel 2016 and Visual Basic for Applications (VBA) platform. The method validation was determined via the accuracy and repeatability of measurements when analyzing HCT and LSP in the Splozarsin Plus tablet and comparing the mean values of their contents in the sample with those analyzed with HPLC. The proposed method is simple with a low cost compared with the standard HPLC method.