Cu(II) and Ni(II) complexes were synthesized through the reaction of 5-bromo isatin and salicylaldehyde with 4-methyl-2-nitroaniline, followed by complexation with metal acetylacetonate (acac). The resulting compounds were characterized using a range of analytical and spectroscopic techniques, including IR, UV-Vis, ^1H NMR, TGA/DTA, and XRD, which indicated that the mixed-ligand complexes adopt an octahedral geometry. In this study, the biological activities of all the synthesized metal complexes and their corresponding ligands were investigated. The compounds were screened against both Gram-positive and Gram-negative bacteria, as well as fungal strains, with results compared to standard drugs and controls. The agar plate disc diffusion method was employed to evaluate antimicrobial activity. The findings revealed that the transition metal complexes exhibited greater biological activity compared to their parent Schiff base ligands.