A closed 3D vesicle polypyrrole-based composite coating (PPy-STi) was electropolymerized on copper with the support of sodium dodecyl sulfate (SDS)-stabilized Ti3C2Tx-MXene via an inverted-electrode cyclic voltammetry route. Due to the promoted polymer nucleation effect of SDS and active catalysis of hydrogen evolution by well-dispersed Ti3C2Tx, a unique vesicle-like architecture of PPy-STi were formed with twisted diffusion pathways, which endowed a strong barrier against aggressive species. Meanwhile the stabilized Ti3C2Tx with high metallic conductivity facilitated the overall electroactivity of PPy-STi coating, yielding much improved anodic protection for copper in artificial seawater (ASW). Relying on the tolerant physical barrier and robust anodic protection capacity of PPy-STi, the coated copper could sustain its passivated state during 10 days of immersion in ASW. The integration of MXenes in conductive polymer coating with enhanced protection characteristics may provide a new strategy to improve the corrosion resistance of electronic devices in the harsh environment.