Developing new antibacterial drugs by using traditional ways is insufficient to meet existing challenges; hence, new strategies in the field of antibacterial discovery are necessary. An alternative strategy is to improve the efficacy of currently available antibiotics. Herein, the antibacterial efficacy of drugs (Cefixime, Sulfamethoxazole, and Moxifloxacin) and drug-loaded cinnamic acid-coated magnetic iron oxide and mesoporous silica nanoparticles (NPs) was elucidated versus Gram-negative bacteria (, neuropathogenic K1 and ) and Gram-positive bacteria (Methicillin-resistant (MRSA), and ). NPs were synthesized by co-precipitation and the Stöber method, and characterized by Fourier transform-infrared spectroscopy, Zetasizer, and Atomic force microscopy. Lactate dehydrogenase (LDH) assays were accomplished to determine drug cytotoxicity against human cells. Spherical NPs in the range of 118-362 nm were successfully synthesized. Antibacterial assays revealed that drugs conjugated with NPs portray enhanced bactericidal efficacies against multiple drug resistant bacteria compared to the drugs alone. Of note, Cefixime-conjugated NPs against K1 and Methicillin- resistant , resulted in the complete eradication of all bacterial isolates tested at significantly lower concentrations compared to the antibiotics alone. Likewise, conjugation of Moxifloxacin resulted in the complete elimination of K1 and MRSA. Of note, nano-formulated drugs presented negligible cytotoxicity against human cells. These results depict potent, and enhanced efficacy of nano-formulated drugs against medically important bacteria and can be used as alternatives to current antibiotics. Future studies and clinical studies are warranted in prospective years to realize these expectations.