Ruthenium and osmium half-sandwich complexes with hydrazinocurcuminoid ligands, 4,4′-((1E,1′E)-(1-(pyridin-2-yl)-1H-pyrazole-3,5-diyl)bis(ethene-2,1-diyl))bis-(2-methoxyphenol) (HZPcurc) and 4,4′-((1E,1′E)-(1-(pyridin-2-yl)-1H-pyrazole-3,5-diyl)bis(ethene-2,1-diyl))diphenol (HZPbdcurc), have been synthesized and characterized using NMR spectroscopy and mass spectrometry. Two of the complexes were also characterized in the solid state using X-ray diffraction analysis, confirming the pseudo-octahedral "threelegged piano-stool" geometry. Density functional theory (DFT) studies are performed on the ligands to evaluate their coordinating capabilities and on the resulting ruthenium and osmium complexes. The complexes are highly soluble in water and stable under physiological conditions. Their cytotoxicity against MCF-7 human breast adenocarcinoma and A2780 human ovarian carcinoma cells, both normal and cisplatin-resistant, was investigated, and good activity and selectivity with respect to nontumorigenic cells (HEK293T) were observed.