Recently, non-steroidal anti-inflammatory drugs (NSAIDs) have been increasingly used in humans and animals. Despite being effective against a wide variety of diseases, they pose a threat to aquatic environments. In the current work, a highly efficient, selective, and sensitive micellar electrokinetic chromatography (MEKC) method was developed for the determination of five NSAIDs in environmental water samples. The optimal separation BGE was 15 mM borate buffer (pH 9), 90 mM SDS, and 10% methanol at a separation voltage of 15 kV and a hydrodynamic injection of 10 mbar for 5 s. The results presented in this study provide a higher number of theoretical plates N > 780 000 with excellent RSDs of 0.1-1.5% and great sensitivity (3-15 μg L-1) for NSAIDs. To validate this method, the solid phase extraction method was optimized using two different cartridges (C18 and Oasis HLB); the results showed excellent recoveries (73-111.6%) for all the analytes in wastewater samples.