Signal　amplification　and　noise　reduction　are　very　crucial　for　the　sensitive　determination　of　disease-related　biomarkers.　The　development　of　rapid　and　laborious　testing　is　urgently　required　due　to　extended　incubation　time　and　high　mortality.　Herein,　we　developed　a　Ce-based　mesoporous　metal-organic　framework-based　multi-enzyme　encapsulation　device　for　the　realization　of　enzyme-linked　immunosorbent　assay　(ELISA)　for　the　dengue　virus　(DENV).　Briefly,　a　UiO-66(Ce)　framework　structure　with　uniform　mesopores　was　synthesized　by　a　one-pot　method,　which　allowed　efficient　encapsulation　of　natural　enzymes　with　an　encapsulation　efficiency　of　700%.　The　developed　multi-enzyme　reaction　probes　were　able　to　maintain　more　than　90%　of　catalytic　activity　stable　at　room　temperature　for　60　days　while　ensuring　efficient　enzyme　immobilization.　Sensitive　evaluation　of　DENV　was　achieved　by　encapsulating　glucose　oxidase　and　horseradish　peroxidase,　combined　with　the　formation　of　an　immune　sandwich　in　the　presence　of　DENV.　The　developed　sensor　enabled　flexible　detection　of　recombinant　dengue　virus　serotype　2　NS1　protein　(DENV2-NS1)　from　0.05　to　100　ng　mL−1,　with　a　low　limit　of　detection　of　39.7　pg　mL−1.　In　addition,　there　were　no　significant　differences　in　the　test　results　of　the　samples　obtained　through　the　developed　multi-enzyme　probes　when　compared　to　commercially　available　ELISA　kits.　This　work　provides　new　horizons　for　the　development　of　efficient　enzyme　encapsulation　systems.　©　2025　RSC.