Objectives: Female population frequently seeks medical consultation for the vaginal candidiasis. Voriconazole (VOR) is a BCS class II antifungal drug with low aqueous solubility and hence inclusion complex was formulated using Hydroxypropyl-β-cyclodextrin (HPβCD). The complex was incorporated into mucoadhesive vaginal tablet using Chitosan and Hydroxypropyl Methyl Cellulose (HPMC K100). Materials and Methods: A 3 2 full factorial design was employed for sustained release tablet using Design expert® software. Results: Scanning Electron Microscopy (SEM) results indicated the complex formation between the drug and HPβCD. The batches showed 39.68±1.2 to 72.31±1.4% of drug release for 4 hr while for 8 hr it was from 77.23±1.5 to 99.82±1.1%. Therefore, the sustained release of drug was achieved for 8 hr. The tablet batches had swelling % from 228.51±12 to 323.11±8% and mucoadhesive strength from 1131.02±49 to 2302.12±55 dyne/cm 2 . In the in vitro antifungal activity study, a higher zone of inhibition was observed for the inclusion complex-based tablet (34±0.3 mm) as compared to plain drug tablet (25±0.4 mm). Conclusion: Therefore, the inclusion complex-based vaginal tablet could be formulated successfully by employing 3 2 full factorial design for increased residence of drug at the vaginal site of infection and for improved therapeutic efficacy.