In this study, natural oyster shell (OS) powder was used to reinforce polyurethane (PU) to fabricate OS powder/PU (OS/PU) composites. First, polycaprolactone diol, 4,4 '-diphenylmethane diisocyanate, and 1,4-butanediol (1,4-BD) were utilized, respectively, as a soft segment, hard segment, and chain extender for PU. Next, the aforementioned chemicals were placed in the solvent N,N-dimethylacetamide (DMAc) to react with each other and form PU. Finally, OSP was added to the PU to form biodegradable OS/PUs. FTIR analysis showed that -NCO functional groups underwent a complete reaction, and X-ray diffraction analysis showed that OS characteristic crystallization peaks emerged when 2 theta = 17.9 degrees, 29.3 degrees, and 34.0 degrees. The TGA, DSC, and DMA showed that increases in OS content elevated PU decomposition temperature, glass transition temperature, and dynamic glass transition temperature. Antibacterial tests showed that increases in the OS content enhanced the antibacterial properties of OS/PUs against Staphylococcus aureus and Escherichia coli.