In the current study, the development of mucoadhesive tablets for buccal delivery of a non-steroidal anti-inflammatory drug was investigated. Binary complexes with piroxicam and cyclodextrins (β-cyclodextrin (β-CD), methylated-β-cyclodextrin (Me-β-CD), and hydroxypropyl-β-cyclodextrin (HP-β-CD)) were prepared by the co-evaporation method. All formulations were characterized by means of differential scanning calorimetry, infrared spectroscopy and powder X-ray diffractometry. Mucoadhesive tablets of binary systems were formulated by direct compression using chitosan as mucoadhesive polymer. The in vitro release profiles of tablets were conducted in simulated saliva and, the drug permeation studies, across porcine buccal mucosa. The results suggest that the rank order effect of cyclodextrins for the drug release was Me-β-CD > HP-β-CD > β-CD, whereas the ex vivo studies showed that the tablets containing chitosan significantly increased the transport of the drug compared to their free complexes. Finally, histological assessment revealed loss of the superficial cell layers, which might be attributed to the presence of cyclodextrins.