Therapeutic nano-bioconjugates (TNBCs) as an advanced class of drug delivery systems have attracted much attention due to more efficacy than the individual medications. Hence, in this study, a novel anti-infection TNBC system is designed based on highly porous silica nanoparticles, gold nanoparticles (AuNPs), and hybridized polyvinyl alcohol (PVA) for the efficient delivery of cefixime (CFM). Furthermore, a conjugation of cysteine-arginine (CR) dipeptide is made onto the surfaces for the enhancement of cell adhesion. Concisely, the AuNPs incorporated inside the PVA network play the key role in the controlled release process triggered by localized surface plasmon resonance (LSPR) heating. The drug content of the CFM-containing cargo (named as CFM@SiO2/PVA/Au-CR) and related release profile have been precisely studied by the confirmed analytical methods. Eventually, confocal microscopy on the stained cells has revealed that the TNBC particles are capable of entering the Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) bacterial cells better than the individual CFM. Also, optical density experiments (OD600) have corroborated that the prepared CFM@SiO2/PVA/Au-CR TNBC includes a high antimicrobial effect on K. pneumoniae and E. coli cells with (93.0 ± 1.5) % and (86.8 ± 1.0) % success rates, respectively, whereas the same dosage of the individual CFM has shown a lower effect on the cell growth rate. Also, estimation of minimum inhibitory/bactericidal concentrations (MIC/MBC) confirmed the enhanced antibacterial property of the CFM through the presented delivery method. Overall, this product is suggested to be clinically administrated instead of the individual CFM due to its high efficacy and containing lower dosage of the antibiotic drug.