The interest in mercury radioisotopes, ^197mHg (t_1/2 = 23.8 h) and ^197gHg (t_1/2 = 64.14 h), has been recently reignited by the dual diagnostic and therapeutic nature of their nuclear decays. These isotopes emit γ-rays suitable for SPECT imaging and Auger electrons which can be exploited for treating small and metastatic tumors. However, the clinical utilization of ^197m/gHg radionuclides is obstructed by the lack of chelators capable of securely binding them to tumor-seeking vectors. This work aims to address this challenge by investigating a series of chemically tailored macrocyclic platforms with sulfur-containing side arms, namely 1,4,7,10-tetrakis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO4S), 1,4,7-tris[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane (DO3S), and 1,7-bis[2-(methylsulfanyl)ethyl]-1,4,7,10-tetraazacyclododecane-4,10-diacetic acid (DO2A2S). 1,4,7,10-Tetrazacyclododecane-1,4,7,10-tetracetic acid (DOTA), the widest explored chelator in nuclear medicine, and the non-functionalized backbone (1,4,7,10-tetrazacyclododecane) were considered as well to shed light on the role of the sulfanyl arms in the metal coordination. To this purpose, a comprehensive experimental and theoretical study encompassing aqueous coordination chemistry investigations through potentiometry, NMR spectroscopy, X-ray crystallography and DFT calculations as well as concentration- and temperature-dependent [^197m/gHg]Hg²⁺ radiolabeling and in vitro stability assays in human serum were conducted. The obtained results reveal that the investigated chelators rapidly complex Hg²⁺ in aqueous media, forming extremely thermodynamically stable 1:1 metal-to-ligand complexes with superior stabilities compared to DOTA or cyclen. These complexes exhibited 6- to 8-fold coordination environments, with donors statically bound to the metal center, as evidenced by the presence of ¹H-¹⁹⁹Hg spin-spin coupling via NMR. A similar octacoordinated environment was also found for DOTA in both solution and solid state, but, in this case, multiple slowly exchanging conformers were detected at ambient temperature. The sulfur-rich ligands quantitatively incorporate cyclotron-produced [^197m/gHg]Hg²⁺ under relatively mild reaction conditions (pH = 7, T = 50°C), with the resulting radioactive complexes exhibiting decent stability in human serum (up to 75% after 24 h). By developing viable chelators and understanding the impact of structural modifications, our research addresses the scarcity of suitable chelating agents for ^197m/gHg, offering promise for its future in vivo application as a theranostic Auger-emitter radiometal.