Simultaneous and selective separation and retention of highly polar Metformin and its combination with other drugs such as moderately polar & hydrophobic drug molecules are difficult by using typical Reverse Phase –High Performance liquid chromatography. Metformin has a very short retention time when separated using RP-HPLC and it may co-elute with the plasma endogenous substances. Extremely polar antidiabetic drug like metformin (MET) along with some drugs often suffer from peak fronting/ tailing effects along with earlier elution with void volume in RP-HPLC. However, Normal phase chromatography is also not useful sometimes due to poor solubility of polar analytes in organic solvents. Therefore, alternative and complimentary technique to this RP-HPLC, is required for the separation of such extremely polar drug.Mixed mode chromatography can be better platform for separation of such types of drug molecules. The use of this newer technique of separations has been increased because of its advantages over traditional separation method for itsefficiency, resolving capacity, specificity, reproducibility and its robustness for lowerdrug concentration. The current work represents a comparative study on two developed and validated chromatographic methods for the simultaneous determination of the ternary mixture (MET, Remo and VIDA) in pure form and in combined tablet dosage. The first method is reversed-phase HPLC using Zodiac C18; column (5µ, 150 x 4.6 mm id)with a mobile phase consisting of 20M m Ammonium acetate buffer and methanol: Acetonitrile (10:90) V/V pH 3 at 230 nm. Chromatographic separation was achieved on an Acclaimed Mix Mode HILIC-1 column (150 mm × 4.6 mm, 5µm) applying an isocratic elution based on 20 mM ammonium acetate- acetonitrile (75:25, v/v) as a mobile phase.Both methods were fully validated following the ICH guidelines in terms of linearity, accuracy, precision, selectivity and robustness.until now no method has been reported for separation of Metformin, Ramogliflozin andVidagliptin.