Abstract Functional textiles that inhibit bacterial proliferation while providing advanced moisture and thermal management are increasingly in demand for regulating personal microclimates and enhancing thermal‐wet comfort. However, traditional wet‐processing technologies face challenges in terms of specific functionalities and limited wash durability, accompanied by severe water waste pollution. In this study, a scalable Janus polyethylene terephthalate (PET) fabric comprising a molecular engineering poly(cation‐π)‐based macromolecule (PXDAG) is developed through an ultrasonic‐assisted spray approach. Density functional theory (DFT) calculations reveals the formation of cation‐π and hydrogen interactions between the PXDAG with cationic nitrogen and aromatic PET, synergistically boosting the antibacterial persistence. The obtained fabric exhibits efficient and sustained antibacterial activity against E. coli and S. aureus (>99.99%), even after 30 wash cycles. Furthermore, the Janus fabrics with PXDAG anchored on one side demonstrates a capacity for directional sweat transport, while maintaining a skin temperature 6.0 °C lower than that of the surrounding environment. Further NMR analysis indicates that intermolecular interactions contributed to robust non‐covalent cohesion and effectively dissipated the fracture energy to improve the interfacial fracture threshold. Combined with the advantages of low cost, eco‐friendliness, and safe operation, the design offers promising solutions for applications in comfortable sportswear, health textiles, and thermal wet comfort.