A four mixed ligand metal complexes derived from the interaction of Cu(II), Zn(II), Zr(IV), and Cd(II) with antihistamine cetirizine.2HCl (Cetz) in the presence of 2,20-bipyridine (Bipy) were synthesized and characterized by using elemental analyses, Fourier transform infrared (FT-IR), UV–visible (UV–Vis), 1H NMR, thermal analysis (thermogravimetric–differential thermogravimetry [TG–DTG]), X-ray diffraction (XRD) analysis, molar conductance, and magnetic moment. The infrared data confirmed that Cetz interacted with metal ion as monodentate ligand through carboxylate oxygen atom, and Bipy chelated through nitrogen atoms. The decomposition mechanism (TG and DTG) for Cetz, Bipy, and their complexes were accomplished, and thermodynamic parameters (Ea, ΔH*, ΔS*, and ΔG*) were determined using Horowitz– Metzger (HM) and Coats–Redfern (CR) methods. The powder XRD analysis of all compounds was carried out to determine the average crystalline size (d) and the nature of the compounds (crystalline or amorphous). The density functional theory (DFT) was achieved to comprehend the optimized geometry for the compounds. All complexes regarded as soft in relation to Cetz, with values ranging from 12.987 to 22.727 eV and equal to 12.658 eV for Cetz. The compounds biological activity was examined against number of bacterial and fungal strains. The data revealed that the investigated complexes have a significant efficiency and may be used as better bactericides.