Introduction: The discovery of azithromycin (Figure 1) as a type of macrolide was very important in the 20th century which was presented as an example of medicinal chemistry and drug design. Recently, azithromycin has a special and interesting profile in this research on pharmacotherapy for COVID-19. Aim and Objective: Synthesis, spectral characterization and thermal analysis of azithromycin complexes with transition metals (Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II)) were discussed. Method: Azithromycin act as a bidentate ligand with the formation of 1:2 (M: L). measurement of magnetism and spectral data shows octahedral structures for all complexes. Result: All of them have Oh geometry and these results are confirmed by Nujol and ESR spectra. Azithromycin act as a bidentate ligand through N (CH3)2 group of dopamine and a hydroxyl group. Also have different sites available for coordination that carries more electronegative charges and the computational study confirms these results. Conclusion: Hyper chemistry program confirmed the binding sites of azithromycin. Azithromycin complexes have higher activity than commercial azithromycin for some strains with the remarkable effect of Zn-azithromycin complex. A molecular approach for COVID-19 was studied.