The aim of this study was to develop a palatable donepezil (DP) orodispersible film (ODF) to facilitate the swallowing process and investigate the effect of cyclodextrin on taste-masking based ondynamic process and invivo drug absorption. Complexation of DP with hydroxypropyl-β-cyclodextrin (HP-β-CD) was applied to mask the bitter taste then the prepared complexes were incorporated into ODF usingsolvent casting method. The taste-masking efficiency was evaluated by e-tongue; meanwhile the pharmacokinetic behavior of DP/HP-β-CD ODF was investigated by invivostudy. Results showed the optimized film was more palatable than donepezil hydrochloride (DH) film and was bioequivalent with DH. The molecular mechanism was revealed by phase solubilitystudy, Fourier-transform infrared spectrometer (FT-IR), Differential scanning calorimeter (DSC), X-ray diffraction (XRD) and molecular modeling. Taste-masking was attributed to the formation ofDP/HP-β-CD which was due to moderate interaction between DP and HP-β-CD. The stability of DP/HP-β-CD was decreased because of the acid environment in stomach, which facilitated the absorption of DP.These results extended our understanding about the application of cyclodextrin complexation and provided guidance for the design of ODF especially for drugs with disgusting taste.