This work has aimed to synthesize less cytotoxic but antibacterial effective materials. Here we synthesized zinc, titanium nanoparticles based multishell hollow spheres (ZnO@TiO2 MSHS) via sequential template approach (STA) and studied their comparative antimicrobial activity with pure zinc and titanium nanoparticles (NPs). Various techniques have been used to explore the physico-chemical properties of the hybrid shells (ZnO@TiO2 MSHS). FTIR, XRD measurements approved the enhanced crystallinity of synthesized hybrid MSHS via STA technique constructed by ZnO, TiO2 NPs. The optical transmittance was enhanced 67.08% for ZnO@TiO2 MSHS where 50.59 %, and 53.32 % of pure ZnO, TiO2 NPs respectively. TEM images showed MSHS made up of zinc and titanium nanoparticles distributed evenly in the structure. The antibacterial activity has been studied and measured via MIZ confirmed that the ZnO@TiO2 multishell hollow spheres exhibit the antibacterial performance. On the other hand the cytotoxicity studies show the cell toxicity was decreased for ZnO@TiO2 MSHS than pure ZnO and TiO2 NPs. So it is recommended that ZnO@TiO2 multishell hollow spheres may be used as a safe and potential antibacterial agent in the field of food packaging, painting, drug delivery and other antibacterial applications.