The use of metal-based species bearing existing pharmaceuticals as ligands, often resulting in enhanced bioactivity, represents an attractive strategy for the development of novel therapeutic formulations. In the context, five well-known non-steroidal anti-inflammatory drugs (NSAIDs) were employed to substitute both PPh₃ and hydride ligands in [Ru(H)₂(CO)(PPh₃)₃] (1), selectively affording, via molecular hydrogen release, neutral κ²-(O,O)-chelate complexes in satisfactory yields. Among the obtained species, two complexes coordinating diclofenac (4) and aspirin (5) were further investigated by single-crystal X-ray diffraction (SCXRD). Preliminary biological studies on the ruthenium-salicylic acid species 2 showed promising antiproliferative activity against HeLa cancer cells, consistent with the fact that NSAID–ruthenium(II) complexes represent a well-established research area for the development of novel anticancer metallotherapeutics.