Candida albicans is the major cause of candidiasis. Better patient compliance and therapeutic efficacy can be achieved by utilizing herbal antifungal agent curcumin which is 2.5-fold more potent than fluconazole at inhibiting the adhesion of C. albicans. Curcumin–hydroxypropyl-β-cyclodextrin (HPβCD) was first developed to increase the solubility of curcumin. The formation of the curcumin–HPβCD complex was characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR) and evaluated for its solubility. Curcumin–HPβCD complex was formulated in a bioadhesive tablets using hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), and Carbopol 934P. A 23 factorial design was applied to investigate effect of polymers on hardness, %swelling, and drug release from tablets. Tablets were characterized by studies of friability, hardness, tensile strength, %swelling, mucoadhesion, in vitro drug release, antifungal activity, and X-ray studies in rabbit. DSC and FTIR data of curcumin–HPβCD indicate that there was complex formation between the drug and HPβCD. Formulations showed 100 % drug release from 5 to 12 h with best results in terms of %swelling and mucoadhesion. In vivo X-ray studies showed that the tablet adheres to vaginal mucosa up to 8 h. The developed curcumin–HPβCD bioadhesive vaginal tablet using 23 factorial design could be a promising safe herbal medication and can ensure longer residence in the vagina and provide an efficient therapy for vaginal candidiasis.