AbstractProton conductive materials are of significant importance and highly desired for clean energy-related applications. Discovery of practical metal-organic frameworks (MOFs) with high proton conduction remains a challenge due to the use of toxic chemicals, inconvenient ligand preparation and complication of production at scale for the state-of-the-art candidates. Herein, we report a zirconium-MOF, MIP-202(Zr), constructed from natural α-amino acid showing a high and steady proton conductivity of 0.011 S cm⁻¹ at 363 K and under 95% relative humidity. This MOF features a cost-effective, green and scalable preparation with a very high space-time yield above 7000 kg m⁻³ day⁻¹. It exhibits a good chemical stability under various conditions, including solutions of wide pH range and boiling water. Finally, a comprehensive molecular simulation was carried out to shed light on the proton conduction mechanism. All together these features make MIP-202(Zr) one of the most promising candidates to approach the commercial benchmark Nafion.