Background: Vaginal candidiasis is one of the most common infections in women. A large variety of antifungal drugs are used for treatment. Sertaconazole (SER) is an imidazole derivative used for treatment of local and systemic fungal infections. Sertaconazole has poor water solubility which affects its dissolution and bioavailability. The objective of this study was to enhance the dissolution and therapeutic efficacy of SER through interaction with certain cyclodextrins (CD) namely HP-?-CD and SBE-?-CD. This could also improve the overall drug efficiency toward C. albicans. In addition, the optimum system in terms of higher in vitro release was formulated into vaginal suppositories and topical hydrogels for maximum effect. Methods: Inclusion complex of SER and CD either HP-?-CD or SBE-B-CD were prepared by physical mixture, ground mixture and co-evaporated at 1:1 and 1:2 molar ratios. Systems were characterized by Fourier Transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and in vitro dissolution studies. SER hydrogels were formulated in different gelling agents and evaluated for their pH, viscosity, homogeneity, in vitro drug release, drug content and antifungal activities. SER vaginal suppositories were formulated using hydrophilic and hydrophobic bases and evaluated for their hardness, disintegration time, drug content, melting point and in vitro drug release. Results: Results obtained from FT-IR, DSC, XRD and in vitro dissolution studies showed that the co-evaporation method was the best method for forming the inclusion complex with the investigated CDs. SER was released from SER/ SBE-?-CD co-evaporate complex at 1:2 molar ratio at a percentage of 93.87%±0.049. Hydrogel 1% and vaginal suppositories of 100 mg SER were successfully formulated and showed SER release of 95.42%±0.148 and 96.31%±0.37 respectively. Conclusion: SER inclusion complex with SBE-?-CD enhanced the dissolution of the drug significantly. In addition, the optimum hydrogel formulation showed significant antifungal activity against C. albicans compared with hydrogel containing SER alone