Membrane distillation (MD) holds significant promise for effluent purification to mitigate the global water shortage. However, the existing petroleum-based MD membranes suffer from high costs, limited sustainability, and wetting issues. Herein, we employed biosynthetic bacterial cellulose (BC) as the substrate and successfully achieved a uniform and stable dispersion of ZnO nanoflowers onto the BC nanofibers through in-situ synthesis technology. After undergoing a fluorination process, a superhydrophobic membrane was prepared by the synergistic effect of micro/nano structures and low surface energy. The resulting membrane exhibited exceptional properties, including a remarkable contact angle of 151.7°, a substantial liquid entry pressure of 2.5 bar, and exhibiting structural integrity and high hydrophobicity even under harsh conditions. Furthermore, this strategy ensured exceptional membrane porosity (∼94.9 %), increased the permeation flux and reduced conductive heat transfer, thereby enhancing the thermal efficiency of the membrane. Furthermore, the membrane demonstrated effective bactericidal activity and self-cleaning capability, facilitating easy cleaning and extending service life. These properties endow the membrane with an impressive durability. After 96 h of continuous operation, the membrane maintained a stable permeation flux of 10.29 L m−2 h−1 and an extraordinary salt rejection rate exceeding 99.9 %. Notably, even with the addition of sodium dodecyl sulfate to the feed, the membrane exhibited stable permeation flux and outstanding antiwetting properties. In summary, the MD membrane fabricated using the bio-inspired chemistry demonstrated a promising potential for long-term applications in direct contact MD operations.