The mononuclear six metal(II) complexes ([Co(mef)2(3-pic)2(CH3OH)2] (1), [Ni(mef)2(3-pic)2(CH3OH)2] (2), [Cu(mef)2(3-pic)2] (3), [Co(mef)2(4-pic)2] (4), [Ni(mef)2(4-pic)2] (5), and [Cu(mef)2(4-pic)2] (6) with mefenamic acid and picoline ligands were synthesized, characterized, and their carbonic anhydrase inhibitory activities were evaluated. The six complexes were characterized by elemental analysis, FT-IR spectroscopy, and thermal analyses. The crystal structures of 1, 3, and 6 were determined by X-ray crystallography. The complexes have octahedral geometry. In 1, the mefenamato ligand behaved as monodentate whereas in 3 and 6, the mefenamato ligand acted as a bidentate ligand. Complexes 3 and 6 consist of the mefenamate and 4-picoline ligands. In 1, unlike the other complexes, methanol acted as a ligand and was involved in the coordination. Carbonic anhydrase I and II isoenzymes were purified from human erythrocytes. The in vitro effects of mefenamic acid, 3-picoline, 4-picoline, and the six metal(II) complexes on these isoenzymes were evaluated.