The Preparation and characterization of Cr(III), Fe(III), Co(II), Ni(II), Cu(II) and Y(III) mixed ligand metal complexes with the effective anti-inflammatory drug tenoxicam (Ten) and 2,2′-bipyridine (Bipy) have been informed in this study by using elemental analyses, FT-IR, UV–Vis., 1H NMR, mass spectra, thermal analyses (TGA, DTG), molar conductance and magnetic moment. FT-IR and UV–Vis. spectra proved that Ten acts as a neutral bidentate ligand chelated to the metal ions via the pyridine-N and oxygen of carbonyl group of the amide moiety and Bipy chelated through the nitrogen atoms. The thermodynamic parameters (E*, ΔS∗, ΔH∗ and ΔG∗) were calculated by using Coats–Redfern and Horowitz– Metzger method from DTG curves. The antimicrobial activity for all compounds against various species of bacteria and fungi was investigated and the results ensured that Fe(III) complex is more active than all other complexes. The DFT calculations were carried out to understand the optimized molecular geometry for the compounds. All studied complexes considered as soft respect to the Ten, with σ value varied from 11.236 to 16.949 eV and equal to 8.772eV for Ten. The anticancer activity was screened against cell culture of HCT-116 (human colorectal carcinoma), HepG2 (human hepatocellular carcinoma) and MCF-7 (human breast adenocarcinoma) for all compounds.