An aqueous thiyl radical-based molecular catalytic system was studied for cis-trans isomerization of maleic acid to fumaric acid at benign reaction conditions. At reaction temperatures higher than 317 K, the initial addition of thiol/thiyl to maleate is the ratedetermining step, whereas the kinetic bottleneck switches to the subsequent elimination with fumarate formation at lower temperatures. Complementary kinetic analysis and DFT calculations support the catalytic reaction proceeds via the radical mechanism, with an activation energy of 50~70 kJ mol -1 for the initial thiyl radical insertion. Chemical mutational investigations showed the structural factors required for better catalysis of the reaction. Thiols are abundant, yet still limited in their practical use for artificial catalysis; in this work, we provide a solid and fundamental basis for better control of thiyl radical chemistry, that will benefit organic radical-based chemical conversions as well as biochemistry.