The purpose of this study was to develop a reversed-phase HPLC method for the simultaneous determination of metformin and pioglitazone in pharmaceutical dosage forms and impurities HPLC profiling of two pioglitazone and three metformin impurities, in the presence of their parent compound. The analytical methods were developed following an optimization from different aspects of the methods available in the correspondent monographs of the European Pharmacopoeia 10.1 edition and that of the United States Pharmacopoeia 43. A C18 column stationary phase and an ion pair former were used to improve the retention of hydrophillic analytes and the most suitable detection wavelength was set at 255 nm. The method was tested by quantitative estimation of active substances from a mixture of commercial tablet powder obtained in a 500:15 metformin:pioglitazone mass ratio. The method for separation of impurities proved to be satisfactory in terms of resolution between peaks, but not in terms of separation efficiency for metformin impurities.