Metal–organic　frameworks,　which　are　the　desired　candidates　for　biosensing　application　due　to　their　tunable　properties,　are　significantly　hindered　by　their　rapid　degradation　in　aqueous　solutions,　as　well　as　the　loss　of　their　inherent　fluorescence.　Most　studies　aim　to　improve　the　hydrophobicity　of　materials　by　modifying　their　contact　angle,　thereby　enhancing　water　stability.　However,　water　droplets　poorly　adhere　to　the　surface　of　hydrophobic　materials,　limiting　their　application　for　direct　contact　and　detection　in　aqueous　environments.　Drawing　inspiration　from　the　sacrificial　protection　mechanism　of　butterfly　wings　used　to　evade　predation　and　entanglement,　a　universal　approach　is　successfully　developed　to　protect　water-sensitive　MIL-MOFs　from　water　molecule　attack　while　preserving　good　hydrophilicity.　Using　the　organic　ligand　2,2′-bipyridine-5,5′-dicarboxylic　acid　(bpydc)　as　sacrificial　protection　scales,　the　MIL-125-NH2-bpydc　demonstrated　broad　pH　structural　stability　(pH　2–12)　and　fluorescence　stability　increased　by　10.17　time　in　aqueous　solutions,　achieving　the　highest　performance　in　MILMOFs.　The　MIL-125-NH2-bpydc　is　biocompatible　enabling　it　to　perform　long-term　fluorescence　imaging　in　living　cells　and　zebrafish,　further　detecting　hydrogen　sulfide　(H2S)　in　the　aqueous　and　biological　systems　via　turn-on　fluorescence　emission.　This　study　offers　a　novel　and　universal　sacrifice-protection　strategy　for　the　design　and　development　of　the　luminescent　biocompatible　MOFs　tailored　for　biosensing　applications.　©　2025　Wiley-VCH　GmbH.