In the paper, the simulation of ship maneuvering in regular waves is accomplished by a simplified six degrees of freedom mathematical model encompassing calm water maneuvering and traditional seakeeping theories. The sliding mode controller with the line-of-sight (LOS) guidance is adopted for the rudder control to steer the ship in waves with the functions of track keeping and roll reduction, in which the design parameters are optimized from genetic algorithm. The nonlinear mathematical model developed here has been proved to be successful by simulating the motion responses of a container ship steering in different heading angle and wave height, and the roll response is indeed reduced by the present sliding mode controller. The present results reveal that the hydrodynamic model and roll reduction technique developed here can be regard as an efficient tool for naval architects to analyze the ship maneuvering behavior with roll reduction by rudder control in waves at the preliminary design stage.