Abstract During the reaction process in lithium–sulfur batteries, Lewis acidic lithium polysulfides (LiPSs) affect ion distribution and overall electrolyte stability, degrading battery performance and product distribution (e.g., Li 2 S). Here, a microenvironment regulation strategy with optimized interface electronics and selective supramolecular channels, is proposed to enhance LiPS reaction kinetics through Lewis basic γ‐cyclodextrin metal–organic framework (γ‐CDMOF). To validate this concept, γ‐CDMOF is rapidly synthesized on 3D graphene foam (GF) via a microwave‐assisted method, resulting in a γ‐CDMOF/GF cathode for high‐performance Li–S batteries. A range of analytical techniques combined with density functional theory (DFT) calculations confirm that introducing a Lewis basic supramolecular microenvironment mitigates the LiPSs shuttle effect, enhances polysulfide capture, and improves sulfur redox conversion. Additionally, COMSOL simulations reveal that the γ‐CDMOF framework and oxygen sites significantly reduce volumetric expansion stress during the LiPS solid–liquid phase transition. Impressively, the γ‐CDMOF/GF cathode exhibits exceptional performance, including a high specific capacity (1253.01 mAh g⁻¹ at 0.1C), excellent rate performance (589.68 mAh g⁻¹ at 5C), and long cycle life (over 1200 cycles). This study introduces a new concept of supramolecular microenvironment regulation and interfacial interaction strategy, offering a unique approach for the development of multifunctional electrode materials.
