Vaterite, a polymorph of calcium carbonate, is gaining attention in nanotechnology as an effective carrier for antifungal agents due to its high surface area, porosity, and biocompatibility. These characteristics enable efficient drug loading and controlled release, allowing antifungal drugs to be delivered more effectively to target sites, potentially enhancing their therapeutic efficacy and reducing side effects. This study explores the synthesis, characterization, and evaluation of Sertaconazole nitrate (SN)-loaded calcium carbonate (CaCO₃) vaterite carrier nanoparticles (NPs) formulated into a topical hydrogel for enhanced antifungal therapy. UV-visible spectroscopy confirmed the synthesis of CaCO₃ vaterite carrier nanoparticles with an absorbance peak at 275 nm. FTIR analysis provided insight into the functional groups present in SN, CaCO₃, and SN-CaCO₃ NPs, indicating successful drug encapsulation. Morphological characterization using SEM and TEM demonstrated uniform, nanometer-sized particles essential for drug delivery. DLS analysis showed a mean particle size of 222.7 nm, with a Zeta Potential of -39.4 mV, suggesting good stability in suspension. Antifungal efficacy was evaluated via well diffusion, showing enhanced inhibition zones for SN-CaCO₃ NPs, with further confirmation from biofilm inhibition assays, highlighting the potential for biofilm-targeted drug delivery. In vitro cytotoxicity assays on A231 skin cancer cells indicated a dose-dependent response, suggesting the need for optimized concentrations in therapeutic applications. The hydrogel formulation displayed desirable physical properties, including appropriate pH, viscosity, spreadability, and washability, suitable for dermatological use. SN-CaCO₃ NPs in a topical hydrogel formulation represent a promising approach for targeted antifungal therapy, particularly for biofilm-associated infections.