Nano polymers have attracted a lot of attention in developing new antimicrobial agents due to their significant advantages. Nanocomposite materials with antimicrobial activity have been widely used in food packaging. The current work introduces efficient nanocomposite; catechol polyurethane foam polymer modified with zinc oxide nanoparticles (PCPU/ZnO) and its application for antimicrobial activity. Catechol polyurethane foam/zinc oxide was synthesized by coupling zinc oxide nanoparticles (ZnONPs) and catechol polyurethane foam polymer (PCPU). The main modifications on the surface of pyrocatechol polyurethane foam/zinc oxide nanocomposite were discussed. The new composite was characterized by ultraviolet-visible spectra (UV-Vis), Fourier transform infrared spectra (FTIR), pH of zero-point charge (PHZPC) and acidic/basic sites. The antimicrobial activity of PCPU/ZnO was tested against G+ve bacterium (Bacillus cereus), Gram-ve bacterium (Escherichia coli) and fungus; A. niger. In vitro agar well-diffusion method showed good inhibition zones of PCPU/ZnO against Escherichia coli (27 ± 0.11 mm), Bacillus cereus (16 ± 0.08 mm) and Aspergillus niger (23 ± 0.14 mm). While PCPU showed a significant antimicrobial effects; with lower inhibition zones against Escherichia coli (20 ± 0.21 mm), Aspergillus niger (15 ± 0.06 mm) and higher inhibition zone against Bacillus cereus (23 ± 0.06 mm).