Buccal candidiasis has become increasingly prevalent in recent years, with Candida albicans being the primary causative organism. While systemic fluconazole is an effective treatment, its use is associated with adverse effects such as gastric upset, hepatic failure, and potential drug interactions. Therefore, the development oflocal fluconazole treatment presents a promising solution to these challenges. This study aimed to formulate an efficient local mucoadhesive film-forming spray for the targeted delivery of fluconazole in the treatment of oral candidiasis. The investigation involved the use of three polymers (hyaluronic acid, polyvinyl alcohol, and xanthan gum) both individually and in combination to identify the most effective formulation. Various tests were conducted to characterize 13 formulations prepared using these polymers, including UV-vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), content assay, drying timeand film formation, viscosity determination, determination of the mucoadhesion strength by turbidimetric methods, drug release study, in-vitro anticandida activity, histological irritation analysis, and stability study. The optimum formula F11, comprised polyvinyl alcohol for its superior mechanical properties and film-forming capabilities, hyaluronic acid, and xanthan gum in combination, exhibiting synergistic mucoadhesive strength. This optimal formulation demonstrated maximum mucoadhesion, rapid film formation, an acceptable spray angle, and controlled release. Furthermore, the optimum formula underwent additional evaluations for in vitro anti-Candida activity, in vivo irritancy assessments, and stability studies, all of which yielded satisfactory results. These findings support the potential of the optimum formula as a straightforward and efficient spray formulation for the treatment of oral candidiasis.