The reaction of [Cp*MCl2]2 (M = Rh/Ir) with N–N′ azine Schiff-base ligands (L1–L4) leads to the formation of mononuclear cationic half-sandwich complexes having the general formula [Cp*M(L)Cl]+ (1–8), (M = Rh/Ir and L = (2-hydroxy-4-methoxybenzylidene)2-pyridylamidrazone (L1), (2-hydroxybenzylidene)2-pyridylamidrazone (L2), (1-(2-hydroxyphenyl)ethylidene)2-pyridylamidrazone (L3) and (1-phenylethylidene)2-pyridylamidrazone (L4). All these complexes were isolated as their hexafluorophosphate salts and fully characterized by spectroscopic and analytical techniques. The molecular structure of complexes (1), (3), (4), (7) and (8) have been determined by single crystal X-ray crystallographic studies which displayed the coordination of the ligand to the metal in a bidentate N∩N fashion through nitrogen atom of pyridine and one azine nitrogen. The chemo-sensitivity activities of the complexes were evaluated against HT-29 (human colorectal cancer) cell line and non-cancer cell line ARPE-19 (human retinal epithelial cells) which revealed that the complexes are moderately cytotoxic to cancer cells over human cells although complex 5 was the most potent among all the compounds. Theoretical studies carried out using DFT and TD-DFT at B3LYP level shows good agreement with the experimental results.