Two-dimensional　nanofluidics　based　on　naturally　abundant　clay　are　good　candidates　for　harvesting　osmotic　energy　between　the　sea　and　river　from　the　perspective　of　commercialization　and　environmental　sustainability.　However,　clay-based　nanofluidics　outputting　long-term　considerable　osmotic　power　remains　extremely　challenging　to　achieve　due　to　the　lack　of　surface　charge　and　mechanical　strength.　Here,　a　two-dimensional　all-natural　nanofluidic　(2D-NNF)　is　developed　as　a　robust　and　highly　efficient　osmotic　energy　generator　based　on　an　interlocking　configuration　of　stacked　montmorillonite　nanosheets　(from　natural　clay)　and　their　intercalated　cellulose　nanofibers　(from　natural　wood).　The　generated　nano-confined　interlamellar　channels　with　abundant　surface　and　space　negative　charges　facilitate　selective　and　fast　hopping　transport　of　cations　in　the　2D-NNF.　This　contributes　to　an　osmotic　power　output　of　~8.61　W　m−2　by　mixing　artificial　seawater　and　river　water,　higher　than　other　reported　state-of-the-art　2D　nanofluidics.　According　to　detailed　life　cycle　assessments　(LCA),　the　2D-NNF　demonstrates　great　advantages　in　resource　consumption　(1/14),　greenhouse　gas　emissions　(1/9),　and　production　costs　(1/13)　compared　with　the　mainstream　2D　nanofluidics,　promising　good　sustainability　for　large-scale　and　highly-efficient　osmotic　power　generation.　©　The　Author(s)　2024.