Low-permeability oil reservoirs are difficult to develop using conventional methods due to their tight characteristics, resulting in low recovery factor. In the Hongliuquan Field of the Qaidam Basin in China, the sandstone reservoirs have low permeability and crude oil viscosity is high, leading to a recovery factor of only 18% with conventional depletion and water flooding methods. To address this issue, a bio-based nanodissolving agent of rock formations was designed and prepared, and its effect on separating the mixture of rock powder and crude oil was experimentally investigated. The results show that the nanodissolver solution can effectively change the wettability of the rock powder, reduce the oil-water interfacial tension, enlarge the rock pores and fractures, thereby significantly improving the oil recovery. After treatment by nanodissolver solution, the crude oil recovery increase from the originally calibrated 18% to over 90%, demonstrating the great potential of enhancing oil recovery. Moreover, field tests also verified its effectiveness in increasing reservoir permeability and reducing the fracturing pressure of water-bearing layers by eroding rock formations.