Objective: To develop and validate novel more sensitive analytical methods for the concurrent quantification of metformin-canagliflozin and metformin-gliclazide in their bulk forms and in their pharmaceutical preparations. Methods: Two methods were developed based on several chemometric assisted spectrophotometric methods and a Reversed-Phase High-Performance Liquid Chromatography (RP-HPLC). The first method applies different spectrophotometric chemometric assisted methods, including ratio difference, derivative ratio and extended ratio subtraction method, while the second method describes a RP-HPLC separation of metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide binary mixtures using a C18 column with a mobile phase consisting of acetonitrile: potassium dihydrogen phosphate (adjusted to pH 3) with sodium lauryl sulphate as additive in the ratio of 30:70 (%v/v) in isocratic elution mode at 1 ml/min. Results: The proposed methods were able to quantify each of the studied drugs in their binary mixtures with high percentage recoveries in both methods. The spectrophotometric methods were able to quantify each of metformin, canagliflozin and gliclazide in the ranges of 2.0-20.0 μg/ml, 1.5-40.0 μg/ml and 2.0-30.0 μg/ml, respectively. The RP-HPLC method produced well-resolved peaks at a retention time of 3.92, 6.92 and 9.10 min in the concentration ranges of 50.0-300.0 μg/ml, 5.0-50.0 μg/ml and 10.0-100.0 μg/ml for metformin, canagliflozin and gliclazide, respectively. The proposed methods were optimized and validated in accordance to the International Conference of Harmonisation (ICH) guidelines in terms of linearity, LOD, LOQ, precision and accuracy. Conclusion: The developed methods were found to be sensitive and reproducible methods for the simultaneous determination of anti-diabetic binary mixtures; metformin hydrochloride-canagliflozin and metformin hydrochloride-gliclazide. And thus were successfully employed for the quality control analysis of the pharmaceutical formulations of the studied binary mixtures.