The problems of environmental pollution are increasingly severe. Among them, industrial wastewater is one of the primary sources of pollution, so it is essential to deal with wastewater, especially oil and water mixtures. At present, biomimetic materials with special wettability have been proven to be effective in oil-water separation. Compared with three-dimensional (3D) materials, two-dimensional (2D) materials show unique advantages in the preparation of special wettable materials due to their high specific surface area, high porosity, controlled structure, and rich functional group rich on the surface. In this review, we first introduce oil–water mixtures and the common oil–water separation mechanism. Then, the research progress of 2D materials in oil–water separation is presented, including but not limited to their structure, types, preparation principles, and methods. In addition, it is still impossible to prepare 2D materials with large sizes because they are powder-like, which greatly limits the application in oil–water separation. Therefore, we provide here a review of several ways to transform 2D materials into 3D materials. In the end, the challenges encountered by 2D materials in separating oil–water are also clarified to promote future applications.