The existence of a moonpool may affect motion characteristics and stability of a drillship. This paper presents numerical and experimental study on the influence of the configuration of a moonpool on the motion performance and stability of a drillship under the condition of a constant displacement. Ship hydrostatics and three-dimensional (3D) potential flow theory are employed to calculate the static stability curves (GZ curves) and motion response amplitude operators (RAOs) of the drillship with conjoined double moonpools, separated double moonpools and single rectangular moonpools, respectively. Numerical model is validated by sea-keeping model tests of the drillship with a conjoined double moonpool carried out in towing tank. It is found that there is a critical heeling angle for the static stability curve of the drillship. The variation of the opening size of the moonpool is found to merely have significant effect on the heave RAOs of the drillship near the piston mode resonance period, while slightly influence on the pitch RAOs near the sloshing mode resonance period. It is demonstrated that smaller or larger openings of the moonpool under a constant displacement can reduce dramatically roll RAOs of the drillship around the natural roll period under bow quartering waves and beam waves, respectively. The coupling effect of roll and heave leading to the heave RAOs decreasing around the natural roll period in beam waves, as well as coupling effect in heave, pitch and roll motion RAOs around the natural roll period in bow quartering waves are observed in the experimental results. The results presented in this study can provide references to the design of the moonpool of a drillship.