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The objective of the experimental study was to developed a validated RP-HPLC analytical method for the simultaneous estimation of gemifloxacin in the presence of atorvastatinGlimepiride and montelukast sodium. The chromatographic analysis involved C18 (5 μm, 25×0.46 cm) column, mobile phase consisted of methanol : water (80:20 v/v with flow rate of 1.0 mL·min−1and pH 3.0 was maintained. Retention time of gemifloxacin , atorvastatin,glimipiride and montelukast was found to be 2.09, 3.5 min , 4.4 min and 7.7 min respectively at 244 nm. The correlation coefficient of gemifloxacin , atorvastatin,glimipiride and montelukast was found to be 0.997, 0.998, 0.998 and 0.998 respectively. The results obtained through the employed method were validated according to the International Conference on Harmonization guidelines requirements. All the validated parameters were of great quality which indicated that the used method could successfully be applied in pharmaceutical preparations. The development of a simple, precise, less time consuming and accurate method is likely to be helpful for routine analysis Key expressions: Gemifloxacin, Atorvastatin calcium,Glimepiride, Montelukast sodium, HPLC, analytical method validation.