The goal of the current effort is to create and analyse a bioadhesive vaginal gel that is loaded with Itraconazole nanosponges to ensure longer residence time at the infection site, providing a favorable release profile for the drug. Methods: Nanosponges was prepared by solvent evaporation method in various ratios of Itraconazole to β-cyclodextrin. Physicochemical evaluation of Naosponges includes determination of Zeta potential, polydispersity, particle size analysis, entrapment efficiency and surface morphology by scanning electron microscopy (SEM). Drug excipient compatibility was established by FTIR and DSC studies. Bioadhesive gel was prepared using Carbopol /Hypromellose /Sodium Carboxymethyl cellulose /HPC, Propyl paraben and methyl paraben was used as a preservative. The pH was adjusted with triethanolamine which resulted in a translucent gel. The optimized Itraconazole nanospoges formulation was dispersed into the gel base. Nanosponges in gel formulations were evaluated for pH, viscosity, spreadability, extrudability and drug content. Ex vivo diffusion studies of the gel was determined on goat vaginal mucosa. In vitro drug release study was performed using cellophane membrane. Results: The optimized batch of IDLNS12 Nanosponges (drug-polymer ratio 1:1) showed entrapment efficiency of 90.44%. Particle size of all the formulations was observed below 310 nm. Regular and spherical particles were observed in the SEM photographs. The optimized gel formulation INSG4 (Carbopol and HPC) showed viscosity of 4464 cps at 2-10 RPM, gel strength recorded as 91.76N load, and spreadability of 35.72 g.cm/seconds. INSG4 showed 99.98% drug release at 12.0 hrs and mucoadhesive time of >12 hr. Conclusion: The study results suggest that Itraconazole- loaded β-cyclodextrin Nanosponges in mucoadhesive gel would provide a mean for sustained treatment of vaginal infections.