We report a novel approach to using a polyurethane scaffold incorporated with cerium oxide nanoparticles as an alternative to the natural enzyme horseradish peroxidase for rapid and reusable detection of hydrogen peroxide. After the preparation of polyurethane from soybean oil and malic acid, cerium or iron oxide nanoparticles were synthesized and incorporated into the polyurethane scaffold by ultrasonic treatment. Formation of nanoparticles was characterized using Fourier transform infrared, transmission electron microscopy, X-ray photoelectron spectroscopy, and energy dispersive X-ray spectroscopy. Iron oxide nanoparticles (FeONPs) with an average size of 50 nm were not uniformly integrated; however, spherical cerium oxide nanoparticles (CeONPs) with an average size of 14 nm were easily incorporated into the polyurethane scaffold. The CeONP-incorporated polyurethane scaffold was highly responsive (<10 s) to H2O2, with a limit of detection of 3.18 μM, and was reusable for at least ten cycles without significant loss of detection activity. However, the response time of CeONP solution was more than 5min. Both FeONP solution and FeONP incorporated polyurethane scaffold were poor at detecting H2O2.