A library of (η 6 ‐p‐cymene)Ru(II) and Ru(II) bis ‐bpy complexes bearing thiazolhidrazinylidene‐chroman‐2,4‐dione was synthesized, characterized, and the molecules are evaluated for their antibacterial activity and cytotoxicity. From this library, several compounds are identified as being active against Methicillin‐resistant Staphylococcus aureus and Methicillin‐sensitive S. aureus . A polypyridyl complex showed a noteworthy minimum inhibitor concentration of 3.1 μ m and no toxicity in healthy eukaryotic cells with a therapeutic index of >32. Active complexes appear to exert their antibiotic activity by affecting both the permeabilization of the bacterial membrane and/or the electron transport chain.