Two ratio derivative spectrophotometric methods were performed for the simultaneous analysis of metformin hydrochloride, empagliflozine, linagliptin, and pioglitazone hydrochloride in their synthetic mixtures without prior chemical separation. The drugs are approved for the treatment of type 2 diabetes. Despite the various advances in the management of diabetes, it remains to be the major cause of disability and morbidity, including blindness, amputation, heart disease, peripheral neuropathy, and kidney disease. These techniques consisted of several steps using ratio and derivative spectra. The absorption spectra of the mentioned drugs were recorded in the range of 200-350 nm, which have the concentration ranges of 1.0-10, 2.5-30, 5.0-40, and 2.5-30 μg mL for metformin hydrochloride, empagliflozine, linagliptin, and pioglitazone hydrochloride, respectively, using zero-order spectra. The mean centring of ratio spectra combined with triple divisor were measured at the amplitude values 242, 256, 272 and 296 nm for metformin hydrochloride, empagliflozine, linagliptin and pioglitazone hydrochloride, respectively; the derivative ratio spectra-zero crossing quantifies the amplitude value of the analytical signal at 234, 244, 260 and 280 nm for metformin hydrochloride, empagliflozine, linagliptin and pioglitazone hydrochloride, respectively. The method was validated according to the ICH guidelines, accuracy, precision and repeatability were found to be within the acceptable limits. Finally, statistical comparisons between the proposed methods and with the reported methods with respect to accuracy and precision show that no significant difference was found by using Student's t-test, the F-test and one-way ANOVA.