To enhance the coalescence separation efficiency of oil/water emulsions, the coalescence mechanism of oil droplets between two media of opposite wettability was investigated. A coalescent-bed comprising a mix of superhydrophobic and superoleophilic quartz sand, along with superhydrophilic and underwater superoleophobic quartz sand, was constructed in a coalescer. Single-factor and response surface experiments were used to study the effects of oleophilic/oleophobic sand mixing ratio, apparent velocity, initial oil concentration, bed thickness, sand particle size on coalescence-separation performance, and to determine the optimal experimental conditions. Employing the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory, the agglomeration mechanism of oil droplets within the mixed particle bed was analyzed based on interfacial energy dynamics. Results indicate that the mixing ratio of the two sands significantly influences coalescence separation performance. An optimal oleophilic/oleophobic sand mixing ratio of 1:1 yielded a mass factor of 0.69 kPa−1, showcasing superior coalescence separation efficiency and an optimal balance of separation efficiency and pressure drop. Under the optimal conditions of apparent velocity of 2.7 m/h, initial oil concentration of 471.9 mg/L, bed thickness of 12.6 cm and mixed sand particle size of 0.5 mm, the oil/water separation efficiency reached 98.08 % ± 0.87 %, with effluent oil droplet size being 2.5 to 3 times larger than at the inlet. Analysis of the oil droplet coalescence mechanism revealed a synergistic effect between the two quartz sands, enhancing oil removal performance. The strong affinity of oil to the superhydrophobic and superoleophilic sand surface increases oil droplet wetting and coalescence efficiency, while the water attraction on the superhydrophilic and underwater superoleophobic sand surface forms a stable water film, improving the flux of the continuous water phase and reducing pressure drop across the bed. This study demonstrates that combining quartz sands of opposite wettability not only overcomes the limitations of single-wettability surfaces in coalescing oil removal but also achieves high efficiency and low energy consumption in oil removal.