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Human fungal pathogen Candida albicans causes oral infectious diseases such as oral thrush in immunocompromised patients with hyposalivation, diabetes mellitus, prolonged use of anti-biotics or immunosuppressive medicines and poor oral hygiene. An anti-fungal medication classified as a BCS class II drug, Clotrimazole has high permeability and low solubility in water. It is commercially available as lozenges, which do not uniformly distribute the drug within saliva for local therapy. This results in higher dose frequency and lower patient compliance. Therefore, in this study we proposed a niosomal based subgingival film formulation of clotrimazole for enhancing drug efficacy by improving drug solubilization capacity and improving patient compliance by prolonging the release of drug at the targeted site and reducing the dose frequency to show effective anti-fungal activity. The prepared niosomal film showed good entrapment efficiency and anti-fungal activity. Niosomal film showed better release pattern than drug loaded film.