Polymethyl methacrylate (PMMA) has garnered significant attention in the field of dentistry due to its wide applications. This paper proposes the incorporation of the nystatin coated copper oxide (CuO) particles having desirable conductivity and antifungal properties, as a filler in the PMMA denture to address their low thermal conductivity, low impact strength, low fatigue resistance, and microbial adhesion. The prepared nystatin coated CuO particles were characterized with several analytical techniques. The nystatin coated CuO particles were mixed in different ratios (0%, 1%, 2%, and 4%) in PMMA corresponding to groups C, E1, E2, and E3, respectively. The prepared samples of composite PMMA with nystatin coated CuO were evaluated to determine their transverse strength, impact strength, Vickers hardness (HV), and thermal conductivity. Furthermore, antifungal properties of CuO particles, nystatin coated CuO particles, and their acrylic composites were evaluated against Candida albicans. Scanning electron microscopy (SEM) analysis confirmed the particles’ spherical and irregular shapes. The particle sizes range from nano to micron level. Fourier‐transform infrared spectroscopy (FTIR) and energy dispersive X‐ray spectroscopy (EDX) analysis confirmed the coating of nystatin on CuO. X‐ray diffraction (XRD) analysis showed the diffraction patterns and planes of CuO monoclinic shape structure. The composite prepared to have higher values of HV (19.53 ± 0.65, 20.16 ± 0.37, and 21.11 ± 0.75, respectively) as compared to the control. The impact strength values were measured high at 14.12 ± 5.55 kJ/m2 for 2% containing nystatin coated CuO acrylic resins compared to control and other groups. The conductivity increased linearly with the addition of CuO particles. The addition of CuO particles causes a reduction in flexural strength as compared to the control group. As the concentration of nystatin coated CuO (1%, 2%, and 4%) in acrylic samples increased, the antifungal properties were improved. Thus, the incorporation of optimized concentrations of nystatin coated CuO particles in acrylic resin resulted in the improved mechanical, thermal, and antifungal properties.