In this study, chemometric-assisted UV-spectrophotometric methods using continuous wavelet transform (CWT) and discrete wavelet transform (DWT) integrated with principal component anal. (PCA) and fuzzy inference system (FIS) were developed for the simultaneous determination of losartan (LOS) and diltiazem (DIL) in binary mixtures and urine samples without any separation process.In the CWT, the best zero crossing point was obtained through the Coiflet wavelet with an order of 2 (coif2) at a wavelength of 218 nm for LOS and Daubechies wavelet with an order of 2 (db2) at a wavelength of 242 nm for DIL.The linearity range was 1-9 μg/mL for LOS, while for DIL it was 6-18 μg/mL.The LOD was 0.5924 and 1.5416 μg/mL, while the LOQ was 1.7951 and 4.5454 μg/mL for LOS and DIL, resp.The anal. of laboratory mixtures using CWT demonstrated mean recovery values equal to 98.07% for LOS and 99.38% for DIL, where the root mean square error was 0.2376 for LOS and 0.2523 for DIL.In DWT, the decomposition of absorption of mixtures was performed using biorthogonal (bior1.5), db2, and Demeyer (DM) at five levels, and their outputs were reduced via PCA.Their output was dimensionally reduced through PCA to serve as the input of the FIS.The wavelet of DM with mean recovery of 100.12% and 100.02%, as well as RMSE of 0.0075 and 0.0105 was selected as the best wavelet for LOS and DIL, resp.The anal. of LOS and DIL in biol. samples using the suggested methods indicated RSD<1.6% and mean recovery >94% and their results were compared to HPLC using the ANOVA test.It can be claimed that these suggested chemometrics methods with the help of spectrophotometry are economical, quick, easy, and reliable ways in quality control laboratories as an alternative to available techniques.