•New Co(II), Ni(II), Cu(II), Zn(II) complexes were synthesized using tridentate Schiff base ligands.•Characterization of synthesized compounds was done using various spectroscopic and physico-analytical protocols.•DFT/BL3YP investigations were performed.•In-vitro antidiabetic potential was tested.•Molecular docking of the most potent analogs was executed in the active site of human pancreatic α-amylase and α-glucosidase. A new series of transition metal complexes of type M(L1-3)(H2O)(CH3COO) where, M = Co(II), Ni(II), Cu(II) & Zn(II), and L1 = 2-(((1,3,4-thiadiazol-2-yl)imino)methyl)-6-ethoxyphenol; L2 = 2-ethoxy-6-(((5-methyl-1,3,4-thiadiazol-2-yl)imino)methyl)phenol; L3 = 2-ethoxy-6-(((5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)imino)methyl)phenol; were synthesized and characterized by various spectral and physico-analytical techniques such as 1H, 13CNMR , FTIR, HRMS, XRD, ESR, TGA, SEM and EDAX. The studies envisaged a penta-coordinated geometry for the complexes, where the Schiff base ligands act in a tridentate manner via the azomethine nitrogen, deprotonated oxygen and one of the nitrogen atom of thiadiazole heterocycle. DFT/B3LYP theoretical method was utilised for calculations of molecular electrostatic potential, HUMO-LUMO energy values of selected compounds. In an in-vitro experiment, the antidiabetic effects of the synthesized compounds were assessed on α-amylase and α-glucosidase enzymes. It was found that compounds 14 and 15 revealed good biological potency with IC50 value close to Acarbose (standard). In-silico study of the synthesized compounds was carried out to check the drug-likeness and it was observed that compounds can be used as orally active drugs. Additionally, molecular docking studies of the potent compounds i.e. 14 and 15, were carried out in the active site of human pancreatic α-amylase (PDB code: 1BSI) and α-glucosidase (PDB code: 5ZCC). A new collection of three Schiff base ligands (1–3) and their twelve Co(II), Ni(II), Cu(II) & Zn(II) complexes (4–15) have been synthesized. The synthesized compounds have been examined for in-vitro antidiabetic study. Display omitted