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Metformin hydrochloride and glimepiride are frequently used in combination for the treatment of type 2 diabetes mellitus and are marketed as fixed dose combination formulations with drastically varying medication concentrations and physicochemical properties. These discrepancies cause difficulties in the development of appropriate analytical processes for the individual and simultaneous determination. The present study deals with the reported analytical methods for metformin hydrochloride and glimepiride in bulk medicines and pharmaceutical dosage forms with special emphasis on UV spectrophotometry and high performance liquid chromatography (HPLC). The UV methods evaluated were direct spectrophotometry, simultaneous equation methods, derivative spectrophotometry, absorbance ratio methods and chemometric approaches. The HPLC methods specifically reversed phase HPLC are discussed in terms of chromatographic separation detection validation performance and application stability indicating analysis. The methods have been compared on the basis of selectivity, sensitivity, linearity, accuracy, precision, robustness, analytical range and practical application. UV spectrophotometric methods are simple, rapid and generally inexpensive to use. HPLC offers improved separation and selectivity for complex mixtures, impurity testing and degradation investigations. The evaluation additionally underlines the demand of superior simultaneous procedures with greener analytical circumstances, systematic method optimization, chemometric strategies and strong stability indicating approaches. Generally, comparative assessment is useful for selection of adequate analytical methods and definition of the perspectives of further development of effective and reliable procedures for quality control of metformin hydrochloride and glimepiride.