As an energy-saving and resistance-reduction device installed on the stern transom plate of the ship, the interceptor has been increasingly applied to medium to high speed ships. A medium-high speed displacement ship in oblique flow is numerically simulated by using the computational fluid dynamics (CFD) software STAR-CCM+ to study the influence of the interceptor and its installation configurations on the hydrodynamic performance of the ship in oblique flow. The calculation results show that the installation of interceptors on both sides reduces the ship resistance by 2.7%~5.9% under the oblique flow condition. However, as the drift angle increases, the improvement of the near-wake flow, such as hollow and rooster tail flow, by the interceptor gradually weakens, resulting in reduced resistance reduction rate of the interceptor. Additionally, the blocking effect of the interceptor on the bottom flow generates high-pressure hydrodynamic loads at the stern, thereby increasing the yaw moment of the ship. It is therefore recommended to deploy interceptors on both sides or only on the lee side during oblique navigation. These findings further reveal the role of the interceptors, which can provide guidance for the decision-making of its use.