Water scarcity significantly promotes the development of membrane technology for seawater desalination; however, the energy consumption of desalination is often enormous. Novel membranes that operated under low temperature are especially attractive for more economic and sustainable water supply. Here, in this work, cyclodextrin-based pervaporation (PV) membranes are fabricated for low-temperature seawater desalination. A molecular-level regulation strategy is developed to fabricate PV desalination membranes by tuning the hydrophilicity and inter-polymer chain distance. Cyclodextrin (CD)-based zwitterions with different molecular size, as the crosslinkers, are used to design a series of PV membranes with different inter-polymer chain distances and hydrophilicity, thus exhibiting diverse PV capabilities. HPAN/CD-Py membrane with the shortest inter-polymer chain distance but the highest hydrophilicity, shows the optimal desalination performance, with a flux of 15.0 kg m⁻² h⁻¹ and salt rejection of 99.98% in treating seawater solution at low-temperature of 25 °C. In addition, the seawater rejection remained steady at a high level with a stable flux and high rejection (99.98%) during the 120 h operation. Our proposed strategy may provide a meaningful instruction to PV membranes, which is promising for seawater or high-salinity water purification.