Abstract The competence to construct sensing platforms capable of selective manipulation in complex biological fluids undoubtedly underpins critical future advances in healthcare. Despite the fact that electrochemiluminescence (ECL) has long been an influential technology for clinical diagnosis worldwide, ECL interface that optimizes fouling resistance has been mimicked less often, especially in an integrated platform. Herein, ECL transducer is prepared by the integration of protonated g‐C 3 N 4 and Ti 3 C 2 T x MXene nanosheets, displaying enhanced charge injection/transfer, and inherent catalytic capacities for coreactant ECL. Mussel‐bioinspired polydopamine was exploited as a thin, surface‐adherent substrate to coat the solid‐state transducer and further initiate secondary reactions via Michael Addition for tailing recognition element and zwitterionic segment. This architecture guarantees not only the least suppression of ECL performance but also desired antifouling properties, ensuring < 7.45% of ECL loss after 96 h of exposure to complex biological fluids. Creatively, a highly integrated platform is equipped with the established biointerface, gas diffusion electrode, and fluidic ECL microreactor, affording high‐performance exosome checking and dynamics tracking in a non‐label manner. Our study provides a general design strategy to obtain a robust antifouling ECL sensing interface based on zwitterionic chemistries and provides a fresh perspective in developing point‐of‐care and implantable ECL devices.