Complex [Os(η6–pcym)(dpa)(VP)]PF6 (1-VP), which contains the histone deacetylase (HDAC) inhibitor valproate (VP), showed ca. 3-fold higher in vitro cytotoxicity against the A2780 human ovarian carcinoma cells than its chlorido analogue; pcym = p-cymene, dpa = 2,2´-dipyridylamine. Complex 1-VP also showed promising selectivity towards the cancer cells (A2780; IC50 = 20.9 µM) over the normal human hepatocytes (IC50 > 200.0 µM). The treatment of the A2780 cells by complex 1-VP led to the induction of apoptosis and production of the reactive oxygen species (ROS), as well as to the mitochondrial membrane potential depletion and cell cycle perturbations. This case study suggests that the replacement of the chlorido ligand of half-sandwich Os(II) complexes by a releasable monodentate biologically active ligand (e.g., VP used in this work) could be an effective strategy for the development of novel non-platinum cytotoxic agents.