In this study, two multivariate calibration methods, including partial least squares (PLS) and principal component regression (PCR), as well as continuous wavelet transform (CWT) along with spectrophotometry technique were developed for the simultaneous analysis of Aripiprazole (ARI) and Quetiapine (QTP) in the pharmaceutical formulation and biological fluid. The linear range of ARI and QTP were 1-3 and 2-10 μg mL-1, respectively for the proposed methods. The root mean square error (RMSE) of ARI and QTP related to the test set was obtained 0.014, 0.0758 and 0.194, 0.882 for PLS and PCR methods, respectively. Also, the mean recovery of ARI and QTP was 99.95, 100.04% and 97.38, 98.83% for PLS and PCR models, respectively. Among various families of wavelets in CWT technique, the Coiflet (Coif3) and Symlet (Sym2) families were selected to determine the value of ARI and QTP, respectively. In this method, limit of detection (LOD) and limit of quantification (LOQ) values were found 0.0033, 0.0200 and 0.2764, 0.3486 μg mL-1 for ARI and QTP, respectively. Mean recovery values of ARI and QTP in synthetic mixtures for CWT approach were 96.98%, 98.94%, respectively. One-way analysis of variance (ANOVA) test was applied to compare the results of both mentioned chemometrics models and high-performance liquid chromatography (HPLC) as a reference method. No significant difference was observed between these methods.