Background: Enforcement of sustainable and green chemistry protocols has seen colossal surge in recent times, the development of an effective, eco-friendly, simple and novel methodologies towards the synthesis of valuable synthetic scaffolds and drug intermediates. Recent advances in technology have now a more efficient means of heating reactions that made microwave energy. Efforts to synthesize novel heterocyclic molecules of biological importance are in continuation. Microwave irradiation is well known to promote the synthesis of a variety of organic and inorganic compounds. The aim of current study was to conceivea mild base mediated preparation of novel Schiff base of 2-Acetylpheno with trimethoprim drug (H2TPBD) and its complexes with Cu(II),Co(II),Zn(II),Cd(II) and Ni(II). Method: The products are likening with traditional processes for reaction time and their yield. (H2TPBD) and the complexes were diagnosed by spectroscopic (Mass, NMR, UV–vis, IR spectral studies, analytical and magnetic data. Results: All complexes were found to be six co-ordinate mono-hydrate as[M(TPBD)(H2O)] [1:1(ligand:metal) ratio] type. The complexes exhibited biological activity against (B.subtilis, P.aeruginosa, C.albicansand Staphylococcus aureus) bacterial strains as compared to (H2TPBD). The antibacterial efficiency showed the following trend: M(II)-complexes ˃ (H2TPBD) ˃ parent drugs. Cu(II), Co(II), Zn(II), Cd(II)andNi(II) complexes had good antioxidant efficiencies than the free ligand (H2TPBD). DNA binding study of complexes with (CT)-DNA utilizing binding nature of the complexes with CT DNA has moreover inveterate by viscometer and emission which then bespoken that complexes bound with CT DNA. The complexestook effective scavenging impact during the DPPH process. Conclusion: [H2TPBD] has been prepared by the condensation of trimethoprim drug and Acetylphenol and characterized by electronic absorption spectra, 1H and 13C-NMR and IR,mass UV-spectroscopies.