Given their versatile nature and wide range of possible applications, core–shell nanoparticles (NPs) have received considerable attention. This paper proposes a novel method for synthesizing ZnO@NiO core–shell nanoparticles using a hybrid technique. The characterization demonstrates the successful formation of ZnO@NiO core–shell nanoparticles, which have an average crystal size of 13.059 nm. The results indicate that the prepared NPs have excellent antibacterial activity against both Gram-negative and Gram-positive bacteria. This behavior is primarily caused by the accumulation of ZnO@NiO NPs on the bacteria's surface, which results in cytotoxic bacteria and a relatively increased ZnO, resulting in cell death. Moreover, the use of a ZnO@NiO core–shell material will prevent the bacteria from nourishing themselves in the culture medium, among many other reasons. Finally, the PLAL is an easily scalable, cost-effective, and environmentally friendly method for the synthesis of NPs, and the prepared core–shell NPs could be used in other biological applications such as drug delivery, cancer treatment, and further biomedical functionalization.