Abstract A series of N ‐alkyl‐ and N ‐aryl‐viologens has been studied in alkaline solutions. In this work, we evaluated the deuteration rate of the viologens in D 2 O solutions of pH values ranging from 7.3 to 12.7. Kinetic experiments and computational calculations showed the high reactivity of H−C(2) bonds toward deprotonation of N ‐aryl‐pyridinium moieties compared to N ‐alkyl‐pyridinium moieties, even in hybrid N ‐aryl/ N ‐alkyl dissymmetric viologens. However this high H−C(2) reactivity in liquid phase contrasted with the proton fragmentation mechanism observed in the gas phase by mass spectrometry. The H/D exchange rate of viologens in very strong alkaline conditions could be significantly reduced using cucurbit[7]uril (CB[7]) as supramolecular protecting group. Ultimately, CB[7] inclusion led to a selective protection of H−C(2) group of N ‐aryl‐pyridinium of dissymmetric viologens, and induced a supramolecular regioselective deuteration.