In this study, oxidized starch hydrogels have been fabricated, and then ZnO nanoparticles were added to swollen oxidized starch hydrogels through the in-situ process. The purpose of this work was to study the effect of ZnO nanoparticles on swelling behavior of oxidized starch hydrogels, as well as investigation their potential to be used in the antibacterial applications. The obtained results showed that the swelling behavior of the nanocomposite hydrogels was dependent on pH conditions. And at pH 7 the highest swelling was observed for samples because of the carboxylate anions created from samples constituent. The ZnO nanoparticles formation in the hydrogels was established with FT-IR spectroscopy, X-ray diffraction and scanning electron microscopy (SEM). SEM micrographs showed the construction of ZnO nanoparticles with a size range of 35-70 nm within the hydrogel matrix. Also, the swelling behaviours of the nanocomposite hydrogels were studied in several pH values and salt solutions. The swelling capacity of the ZnO nanocomposite hydrogels was reliant on the abundance of the zinc oxide nanoparticles in the oxidized starch hydrogels matrix. Furthermore, these oxidized starch/ZnO nanocomposite hydrogels showed smart swelling behaviours in NaCl, CaCl and AlCl aqueous solutions and their swelling ratio reduced with a growth of the salt concentration and valence of the cations. The swelling capacity for the resulted compounds in diverse salt solutions with the equal concentration was in order of NaCl > CaCl > AlCl. Also, the antibacterial activities of the ZnO nanocomposite hydrogels were proven against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The nanocomposite hydrogels confirmed fine antibacterial properties. The developed oxidized starch/ZnO nanocomposite hydrogels have the potential to be used for biomedical use.