<p>Guanidine compounds constitute a significant class of nitrogen-containing organic molecules with widespread applications in medicinal chemistry and synthetic science. Herein, we report a copper-catalyzed desulfurization strategy for the efficient synthesis of guanidine derivatives directly from amines and carbon disulfide. This transformation hinges on the in situ generation of a thiourea intermediate of a thiourea intermediate, followed by copper-catalyzed desulfurization to afford a highly reactive carbodiimide intermediate, with molecular oxygen serving as a green terminal oxidant in the catalytic cycle. In contrast to conventional methodologies relying on hypervalent iodine reagents, this protocol circumvents the use of strong oxidants and exhibits broad substrate scope and excellent functional group tolerance. Notably, this approach is amenable not only to the construction of structurally diverse and complex guanidine derivatives but also to the late-stage functionalization of drug-related molecules.</p>