A series of the new ruthenium(II) complexes with different number of aldehyde groups have been synthesized and characterized for the simple and selective sensing of homocysteine (Hcy) and cysteine (Cys). The reaction of these ruthenium(II) complexes with Hcy and Cys afforded thiazinane or thiazolidine derivatives which resulted in the obvious changes in the UV-visible spectra and strong enhancement of the luminescence intensity of the system. The luminescence enhancement of [Ru(dmb)(2)(L2)](2+) (dmb: 4,4'-dimethyl-2,2'-bipyridine) showed a good linearity in the concentration of 4.2-350 μM and 6-385 μM with the detection limits of 0.3 μM and 1 μM for Hcy and Cys, respectively. The absorption and emission bands from metal-to-ligand charge transfer transition in the visible region and the large Stokes shift of the ruthenium(II) complex chromophore made it suitable for biological applications.