Core@shell structured nanocomposites have received significant attention for providing a combinatory antibacterial mode of action. A rational identification of the accommodated unit’s role in the core@shell nanostructure is needed in order to solidify whether antibacterial synergism could be provided within the same core-shell structure against bacterial cell growth. Herein, a novel nanostructure(s) composed of a cerium oxide core and a porous silica shell (CeO2@pSiO2) with curcumin and lectin accommodation was prepared, and the antibacterial synergism provided by the nanocomposite was identified. The resulting spherical-shaped nanostructure CeO2@pSiO2 allowed the accommodation of curcumin loading (9 w/w%) and lectin (concanavalin A) coating (15 w/w%). The antibacterial synergism was tested using a minimal inhibitory concentration assay against Escherichia coli gram-negative bacterial strain. Furthermore, the bacterial cell disruption mechanisms induced by the curcumin-loaded and concanavalin A-coated CeO2@pSiO2 core@shell structure, namely the nanoantibiotic (nano-AB) and its design components were identified individually. Our findings revealed that mesoporous silica shell around the cerium oxide core within the nano-AB design aiding the accommodation of curcumin and concanavalin A promoted the destruction of the motility of the bacterial cells and the permeability of the inner and outer bacterial cell membranes. Our findings strongly indicate the promising potential of a mesoporous silica shell around cerium oxide core nanoparticles to provide synergistic antibacterial treatment and attack the bacterial cells by different action mechanisms.