The reactions of the dimeric complexes [RuX(η--cymene)] (X = Br, I, SCN) with L-proline (ProH) and -4-hydroxy-L-proline (HypH), in methanol in the presence of NaOH, afforded [RuX(κ,-Pro)(η--cymene)] (X = Br, 1b; I, 1c; SCN, 1d) and [RuX(κ,-Hyp)(η--cymene)] (X = Br, 2b; I, 2c; SCN, 2d), respectively. Alternatively, the one-pot, sequential addition of the appropriate α-amino carboxylate and X salt to [RuCl(η--cymene)] led to [RuX(κ,-Pro)(η--cymene)] (X = N, 1e; NO, 1f; CN 1g) and [Ru(N)(κ,-Hyp)(η--cymene)] (2e). Complexes [Ru(κ,,'-OCCH(NH)(R)O)(η--cymene)] (R = CH, 3h; R = CHMe, 4h; R = CHCH, 5h) were prepared from the reaction of [RuCl(η--cymene)] with the appropriate α-amino acid and NaOH in refluxing isopropanol. Treatment of the L-serine (SerH) derivative [RuCl(κ,-SerH)(η--cymene)] (3a) with 1,3,5-triaza-7-phosphaadamantane (PTA) in water at reflux produced [Ru(κ,-Ser)(κ-PTA)(η--cymene)]Cl ([3i]Cl). The products were isolated in good to excellent yields, and were characterized by elemental analysis, IR and multinuclear NMR spectroscopy. The structures of 1f and 2b-e were ascertained by X-ray diffraction studies. The behaviour of the complexes in water and cell culture medium was investigated by multinuclear NMR and UV-Vis spectroscopy, revealing a considerable influence of the monodentate ligand on the aqueous chemistry. Complexes 1d-e, 2d-e, 3h, 4h and [3i]Cl, showing substantial inertness in aqueous media, were assessed for their cytotoxicity towards A2780 and A2780cisR cancer cell lines and the noncancerous HEK 293T cell line. A selection of compounds was also investigated for Ru uptake in A2780 cells and interactions with cytochrome c as a model protein. Combined, these studies provide insights into the previously debated role of the '' ligand on the biological activity of Ru(II) arene α-amino acid complexes.