A novel cefotaxime derivative, Schiff base ligand, is used to create copper complex. Molar conductivity, elemental study, Infrared, uv-vis spectra, magnetic moment, and thermal behavior are used to describe the complex. The compound molar ratio is discovered to be one metal to one ligand. The infrared bands show that the Schiff base binds copper ion as tridentate via carboxylate, acetylacetone carbonyl and imine group.The magnetic moment, uv-vis transitions, and ESR spectrum, on the other hand, show that the CuII-complex structure is octahedral. Thermal analysis also reveals the presence of water and methyl alcohol in the compound. Moreover, Sol-gel process is utilized for silica nanoparticles preparation. While, the complex is loaded on silica nanoparticles after surface modification. Whereas, the CuII-complex and nano-complex are tested for Gram (+) (B. subtilis and S. aureus) and Gram (-) (E. coli and P. aeruginosa) microbes. The biological results exposed that the synthesized complex has high potential to overcome the resistance of microbes.