This study aims to prove the complexation of cefpodoxime proxetil (CP) by hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in the presence of sodium carboxymethyl cellulose (Na CMC), and makes a comparison of commercial tablets by dissolution and antimicrobial activity studies. The CP-HP-beta-CD complex was prepared by kneading method and characterized by SEM, FTIR and DSC. The solubility method was used to investigate the effect of HP-beta-CD and Na CMC on the solubility of CP. The complex tablets were prepared using direct compression method. Dissolution studies were performed with complex tablets and commercial tablets in pH 1.2, 4.5, 6.8 and 7.4 buffer solutions. It was observed that complexation occurred in all formulations, and HP-beta-CD is able to increase CP solubility and dissolution rate of CP was improved from complex tablets, when compared with commercial tablets. Furthermore, the antimicrobial activity studies revealed that the CP-HP-beta-CD complex and complex tablets were shown to have more effective antimicrobial activity than commercial tablets. It is evident from the results that complexation with HP-beta-CD in the presence of Na CMC is feasible way to prepare a more efficient tablet formulation with improved dissolution and antimicrobial activity.