This study describes the synthesis, characterization, pharmacokinetic profiling, and antimicrobial activity of a Schiff base ligand derived from sulphamethazine and 4- diethylaminosalicylaldehyde (SMT-DEAS) and its CO (II), NI (II), CU (II), and MN (II) complexes. The ligand and complexes were obtained in good yields (78–86%) as stable, non-hygroscopic solids with melting/decomposition points of 185–192 °C and 265–284 °C, respectively. Elemental analysis and AAS confirmed a [ML₂]·nH₂O stoichiometry, while low molar conductance values (9.62–14.75 Ω⁻¹ cm² mol⁻¹) indicated non-electrolytic behavior. FTIR spectra revealed coordination through azomethine and phenolic oxygen atoms, with new M–N/M–O bands at 420–580 cm⁻¹, and UV–Vis/magnetic data supported tetrahedral geometry for all the complexes. Antimicrobial studies showed enhanced potency of the complexes compared to the free ligand, notably Co(II) and Cu(II) against Staphylococcus aureus (20–22 mm inhibition zones) and Mn(II) against Aspergillus niger (18–20 mm). Pharmacokinetic predictions revealed SMTDEAS (MW 438.5 g/mol, Log S –7.11, TPSA 120 Ų) complied with Lipinski’s rule and showed high gastrointestinal absorption, Whereas its complexes (MW 960–970 g/mol, Log S –15.8, TPSA up to 227.6 Ų) exhibited reduced solubility, low GI absorption, Pglycoprotein interaction, and minor leadlikeness violations. All compounds lacked PAINS alerts, though Brenk alerts linked to aniline substructures suggested potential toxicity risks