Chemical　warfare　agents　represent　a　severe　threat　to　mankind　and　their　efficient　decontamination　is　a　global　necessity.　However,　traditional　disposal　strategies　have　limitations,　including　high　energy　consumption,　use　of　aggressive　reagents　and　generation　of　toxic　byproducts.　Here,　inspired　by　the　compartmentalized　architecture　and　detoxification　mechanism　of　bacterial　micro-compartments,　we　constructed　oil-in-water　Pickering　emulsion　droplets　stabilized　by　hydrogen-bonded　organic　framework　immobilized　cascade　enzymes　for　decontaminating　mustard　gas　simulant　(2-chloroethyl　ethyl　sulfide,　CEES)　under　sweet　conditions.　Two　exemplified　droplet　systems　were　developed　with　two-enzyme　(glucose　oxidase/chloroperoxidase)　and　three-enzyme　(invertase/glucose　oxidase/chloroperoxidase)　cascades,　both　achieving　over　6-fold　enhancement　in　decontamination　efficiency　compared　with　free　enzymes　and　＞99%　selectivity　towards　non-toxic　sulfoxide.　We　found　that　the　favored　mass　transfer　of　sugars　and　CEES　from　their　respective　phases　to　approach　the　cascade　enzymes　located　at　the　droplet　surface　and　the　facilitated　substrate　channeling　between　proximally　immobilized　enzymes　were　key　factors　in　augmenting　the　decontamination　efficacy.　More　importantly,　the　robustness　of　immobilized　enzymes　enabled　easy　reproduction　of　both　the　droplet　formation　and　detoxification　performance　over　10　cycles,　following　long-term　storage　and　in　far-field　locations.