Polymeric mixing and ultrasonic dispersion method as a green, fast, effective, and inexpensive technique was utilized to prepare epoxy/polyurethane/zinc manganite nanoparticles (EP/PU/ZnMn2O4 NPs) nanocomposites. The ZnMn2O4 NPs and PU were used for the optimization of mechanical properties of EP resin. Response surface methodology (RSM) coupled with central composite design (CCD) was employed to obtain suitable mathematical models as function of physico- and thermomechanical factors. The weight fractions of PU and ZnMn2O4 NPs were chosen as the independent variables, and the effect of these variables on the mechanical properties of the EP resin was investigated. The tensile test showed that the addition of the PU and ZnMn2O4 NPs in the polymer matrix improved the mechanical properties. The dynamic mechanical analysis results showed that the storage modulus and the glass transition temperatures of the nanocomposites increased and decreased, respectively. The optimum values of PU and ZnMn2O4 NPs contents for good mechanical properties were determined as 0.73 weight percentage (wt%) and 0.15 wt% ratio to EP resin, respectively. The antibacterial properties of the optimum sample were also investigated, and the results showed that, with the addition of the NPs, the antibacterial performance of EP/PU increased. The X-ray diffraction, Fourier-transform infrared, scanning electron microscopy/energy-dispersive X-ray analysis, diffuse reflectance spectroscopy (DRS), and vibrating sampler magnetmeter analyses were also applied to study the chemical and magnetic properties of the optimized nanocomposite samples.