Viologen is investigated as the anolyte in pH-neutral aqueous flow batteries. The full utilization of two electrons is essential to achieve a high specific capacity, which is, however, seriously limited by the proton attack of the two-electron reduced viologen. In this work, a redox-modulated host–guest complex strategy is developed to address the above issue by introducing hydroxyethyl-β-CD (HE-β-CD) in the 1-methyl-1′-[3-(trimethylammonio)propyl]-4,4′-bipyridinium trichloride ((MAPVi)Cl3) solution. The oxidation state (MAPVi3+, MAPVi2+) stays in water and is electrochemically active in the redox transition. The two-electron reduced state (MAPVi+) turns hydrophobic and self-adapts in HE-β-CD’s cavity via a host–guest interaction; therefore, MAPVi+ can be well-protected against the proton attack. To demonstrate the effect, an aqueous flow battery is tested with (MAPVi)Cl3 as the anolyte and 2,2,6,6-tetramethylpiperidin-1-oxy derivative as the catholyte. A 500 cycle test shows that the capacity decay rate is 0.22% per cycle for a mere 0.10 M (MAPVi)Cl3 and 0.05% per cycle for 0.10 M (MAPVi)Cl3 + HE-β-CD. A higher concentration of 0.30 M (MAPVi)Cl3 + HE-β-CD delivers a specific capacity of 14.1 Ah L–1 and an energy efficiency of 82% at 40 mA cm–2 with superior cycling stability over 100 cycles. This work provides a facile supramolecular chemistry strategy for stabilizing electroactive compounds in aqueous flow batteries.