Natural polysaccharide/clay matrices offer a promising route for developing topical drug delivery systems with improved hydration, structural cohesion, and controlled release. This study reports, the development of a white angico gum/bentonite biocomposite as a carrier for tioconazole delivery. The originality of the work lies in the use of an underexplored Brazilian native polysaccharide combined with bentonite to obtain a hybrid platform capable of integrating drug accommodation, medium-responsive swelling, antifungal activity, and preliminary biocompatibility. The biocomposite was prepared from purified angico gum and bentonite, loaded with tioconazole, and characterized by SEM, XRD, MICRO-CD, FTIR, TG/DTG, DSC, wettability, swelling, release kinetics, antifungal assays, Artemia salina toxicity screening, HET-CAM, and hemolysis tests. The material exhibited cohesive morphology, preserved gum/clay chemical features, thermal stability, hydrophilic behavior, and medium-dependent swelling. Tioconazole incorporation reached approximately 75%, and drug release was sustained over 30 h, reaching 15.79%, with the Weibull model providing the best kinetic fit. The loaded biocomposite showed enhanced antifungal performance, with an MIC of 8 µg mL⁻¹ against C. albicans, outperforming free tioconazole. HET-CAM and hemolysis assays indicated non-irritant and hemocompatible behavior. Overall, the angico gum/bentonite matrix represents a sustainable and functional platform for topical antifungal delivery.