A simple, efficient, environmentally friendly, and cost-effective method using microwave irradiation in a green medium was employed to synthesize a series of octahedral Ni(II) complexes with an NOO′N donor ligand. The primary bi-anionic tetradentate ligand used was o-phenylene-bis(o-hydroxyacetophenone) diamine, while various monodentate secondary ligands such as quinoline and pyridine were also incorporated. All the eco-friendly synthesized complexes were thoroughly characterized by elemental analysis, conductivity and magnetic moment measurements, and spectroscopic techniques. The results obtained were compared with those from conventional synthetic methods. Evaluation of antimicrobial activity for the ligand and its Ni(II) complexes revealed that the metal complexes exhibit significantly higher activity than the free ligand against the tested microbial strains.