ABSTRACT The membrane‐based reverse electrodialysis (RED) is considered as the most promising technique for salinity‐gradient energy harvesting. However, the high cost and difficult processing of traditional membrane materials usually limit their development in the field. Herein, a salinity‐gradient cell is constructed based on a group of anion‐ and cation‐selective 2D clay nanofluidic membranes. The opposite surface charge and confined 2D nanofluidic channels contribute to the opposite ion selectivity of the two membranes. For constructing the salinity‐gradient cell, a superposed electrochemical potential difference is created by complementing the diffusion of oppositely charged ions, and an output power density of up to 5.48 W m −2 can be obtained at a salinity gradient of 0.5/0.01 M NaCl without the contribution of electrode material redox reaction, superior to other existing natural nanofluidic RED systems to our best knowledge. Furthermore, the output voltage of the cell can reach 1.8 V by connecting 15 tandem LM‐RED stacks under artificial seawater and river water, which can power the electronic devices. According to detailed life cycle assessments, the fabrication of 2D clay nanofluidic pairs achieves a significant reduction in resource consumption by 90%, a decrease in greenhouse gas emissions by 90%, and a notable reduction in production costs by 67% compared with the classical 2D nanofluidics, promising good sustainability and paves the way for clay‐based membranes in RED devices for the salinity‐gradient energy harvesting.