As an alternate physical technique, laser ablation is considered a promising and effective route that may be used for the creation of nanoparticles. The main goal of this study is to synthesis CuO/ZnO/Al2O3 nanoparticles in aqueous media using laser ablation route in deionized water (DIW), to be used for the synthesis of 2-cyano-2-( p - nitrobenzylidene)- p -methoxyacetanilide via Knoevenagel condensation reaction between p-nitrobenzaldehyde and 2-cyano-N-(4methoxyphenyl) acetamide compounds. This protocol was used to obtain a high yield of the final product. The method is considered solvent-free, eco-friendly, short-time reaction, and excellent yield in comparison with that using catalyst in the bulk form. The antibacterial properties of the synthesized products were evaluated against Gram-positive (Streptococcus bacteria) and Gram-negative bacteria (Enterococcus bacteria).