A series of transition metal complexes of alloxan monohydrate (H2L1) and ninhydrin (H2L2) have been prepared where metal ions are Fe(III), Co(II), Ni(II), Cu(II), Zr(IV), and Mo(VI). Different microanalytical techniques, spectroscopic methods, and magnetic studies were applied to assign the mode of bonding and elucidate the structure of complexes. All solid complexes are of 1:1 (M:L) stoichiometry and octahedral geometry except nickel (II) complexes exist in a tetrahedral geometry. FTIR spectral interpretation reveals that HL1 coordinates to the central metal ion in a bidentate ON pattern, whereas HL2 behaves as an alterdentate ligand through hydroxyl oxygen and carbonyl oxygen either C(1) = O or C(3) = O. The thermal behavior of some complexes was followed up to 700 °C by different techniques (TGA, DTA, and DSC) where decomposition stages progress in complicated mechanisms and are ended by the formation of metal oxide residue. Besides, biological screening involving antioxidant, antibacterial, and antifungal for ligands and some of their complexes was done. Moreover, four examined metal complexes displayed anticancer activity against hepatocellular carcinoma cells (HepG-2) but to different degrees. According to the IC50 values, Cu-ninhydrin complex, [Cu(HL2)(H2O)4].Cl has a better potency impact in comparison with cisplatin which was used as a reference control. This is in harmony with the molecular docking simulation outcomes that predicted a good binding propensity of the Cu-ninhydrin complex with hepatocellular carcinoma protein (2jrs). Therefore, the Cu-ninhydrin complex should be deemed as a potential chemotherapeutic agent for hepatocellular cancer. Graphical Abstract