Adsorption of proteins onto the capillary wall leads to poor performance when capillary electrophoresis frontal analysis (CE-FA) is used for determination of drug-protein binding parameters.Herein, we described a method to reduce such adsorption by coating the capillary with polyelectrolyte multiple layers, which was simply created by alternatively flushing the capillary with positively charged polyelectrolyte polybrene (HDB) and negatively charged polyelectrolyte dextrin sulfate (DS).Human serum albumin (HSA)-(S)-ibuprofen system was selected as the experiment model to evaluate the coating efficiency.Compared with the uncoated capillary, the reproducibility in terms of the EOF and the plateau peak height of ibuprofen was obviously improved.Moreover, the plateau shape was also improved to permit more accurate measurement of the binding parameters.It was demonstrated that the coating had no significant interference with the measured protein-drug binding parameters.Coating the capillary with polyelectrolyte multiple layers is a simple and effective way to improve the performance of CE-FA.