In this study, the filler–matrix interactions are assessed in two nanocomposites having different antibacterial activity. The two polymers used as matrix are poly(amide) 6 (PA6) and low-density poly(ethylene) (LDPE). The filler, zinc oxide (ZnO) nanoparticles, with a content as low as 1 w/w% in the polymers showed great antibacterial activity against Escherichia coli and Staphylococcus aureus. However, the bacterial slaying capability of composites was found better when ZnO was dispersed in PA6, where the efficiency is similar to pure ZnO particles. The dispersion of ZnO and its interactions with the matrix have been investigated by means of scanning electron microscope, rheology, thermogravimetric analysis and differential scanning calorimeter. This study shows stronger interactions of ZnO particles with LDPE, which could have an effect on final antibacterial properties.