Designing tailored multifunctional catalysts that enhance lean-electrolyte sulfur redox kinetics is crucial for achieving high-energy-density lithium–sulfur batteries; however, it still remains challenge. Motivated by the structural protection of active sites in natural enzymes, we implant natural glutathione (GSH) within the metal–organic framework MIL-47 (V) cavity for GSH@MIL-47 (V) biomimetic catalysts, thereby stabilizing and activating its thiol functionality. Quantification using 5,5’-dithiobis(2-nitrobenzoic acid) (DTNB) as a probe confirmed successful GSH incorporation, revealing that GSH@MIL-47 (V) enables a continuous and stable catalytic reaction cycle. Moreover, in-situ and ex-situ spectroscopies indicate thiol-driven S–S bond breakage that lowers the reaction energy barrier and concurrently promotes lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) decomposition. As a result, GSH@MIL-47 (V) cells, at 6 C rate, deliver a discharge capacity of 733.1 mAh·g⁻¹ and maintain 573.0 mAh·g⁻¹ after 750 cycles. Even under an electrolyte-to-sulfur ratio of 5.5 μL·mg⁻¹, it maintains 867.2 mAh·g⁻¹ at a high-rate of 0.5 C. This strategy highlights the potential of enzyme-inspired catalysts for enhancing lithium–sulfur batteries.