Purpose <p>This study aimed to fabricate and investigate the characteristics of sodium caseinate (SCA)-clay composite films loaded with fluconazole (FLU) for localized drug delivery. The clays used were magnesium aluminum silicate (MAS) and halloysite (HAL).</p> Methods <p>A continuous thin film was prepared using a conventional film-coating pan and a spraying method. The FLU-loaded SCA-clay films, with different SCA: clay ratios, were evaluated regarding surface and matrix morphology, molecular interaction, crystallinity, mechanical properties, film dissolution, drug release, antifungal activity, and mucoadhesive properties.</p> Results <p>The clays, SCA, and FLU interaction primarily occurred through hydrogen bonding. MAS presented a stronger interaction with FLU than HAL. The FLU polymorphism in the films was identified as the monohydrate form. The clay addition did not affect the drug’s polymorphism or the mechanical properties of the films. The film dissolution time of the FLU-loaded SCA films was 7.9&#xa0;min, and the addition of HAL caused a negligible effect on this parameter. In contrast, the FLU-loaded SCA-MAS films presented longer than 1&#xa0;h of film dissolution time because they could form nanocomposites with SCA in the films. As a result, the FLU released from the films provided a greater T_50% value when blended with MAS. The released FLU exhibited effective antifungal activity against <i>Candida albicans</i>. Additionally, the films retained mucoadhesive properties on porcine mucosa with the clay additions.</p> Conclusions <p>This study suggests that MAS can enhance FLU-loaded SCA films by extending their dissolution time and drug release, indicating their potential as a local delivery system for oral candidiasis.</p> Graphical Abstract <p></p>