Methyl picolinate (Mepic) is a starting material in the synthesis of several organic materials and enzymes. Notably, Mepic-ligand-based complexes with metals such as Zn(II), Cd(II), Ru(II), and Rh(III) have garnered attention for catalysis; however, Ru(II)–Mepic complexes remain structurally unexplored. In this study, trans(Cl)-[RuCl₂(dmso-S)₂(Mepic)]·0.25H₂O (1·0.25H₂O, dmso = dimethyl sulfoxide) was produced in a satisfactory yield (80%) via the reaction of trans(Cl)-[RuCl₂(dmso-S)₄] with neutral N,O-ligand Mepic in methanol (MeOH) at room temperature. The use of picolinic acid (Hpic) instead of Mepic in H₂O-ethanol (EtOH) produced the corresponding complex—trans(Cl)-[RuCl₂(dmso-S)₂(Hpic)]·H₂O (2·H₂O)—with a slightly higher yield (82%). Crystal structure analysis of 1·0.25H₂O and 2·H₂O revealed that each chelating ligand coordinated to Ru²⁺ via pyridyl-N and carbonyl-O atoms and Hpic acted as a neutral bidentate ligand in 2. In DMSO, 1 was labile and released Mepic to form [RuCl₂(dmso)₄], owing to the hemilability of N,O-ligand Mepic. In contrast, 2 was inert in DMSO because H⁺ was released from Hpic in solution, forming the anionic mono(pic)Ru complex—trans(Cl)-[RuCl₂(dmso-S)₂(pic-κ²N,O^–)]⁻. ¹H NMR and UV-Vis spectroscopic studies showed that 2 also generated the anionic mono(pic)Ru complex in aqueous solutions. Although free Mepic is inert in water, 1 underwent thermal hydrolysis in water to produce free MeOH. The dissociation of monodentate ligands was also observed in the thermal hydrolysis of 1. Thus, it was a complicated reaction. The reaction of 1 with equimolar OH⁻ in water quickly and selectively yielded the same complex and a MeOH molecule. Our study will assist in assessing the catalytic potential of this complex and related systems.