The first examples of (arene)Os(II) curcuminoid derivatives have been prepared and characterized. The neutral complexes [(p-cym)Os(curc)Cl] (1) and [( p-cym)Os(bdcurc)Cl] ( 2), together with the cationic derivatives [( p-cym)Os(curc)(PTA)][SO3CF3] (3) and [( p-cym)Os(bdcurc)(PTA)][SO3CF3] (4) (PTA = 1,3,5-triaza-7-phosphaadamantane) were characterized by NMR spectroscopy and ESI mass spectrometry, and the crystal structure of 1 was determined by X-ray diffraction analysis. The cytotoxicity of the complexes was evaluated in vitro against human ovarian carcinoma cells (A2780 and A2780cisR), as well as against non-tumorous Human Embryonic Kidney cells (HEK293). Binding of the complexes to potential pharmacological targets and serum carriers was also explored.