To address the system uncertainties and bilateral drive synchronization issues of a stepper motor-driven XY platform, a self-disturbance rejection control strategy based on deviation self-coupling compensation is proposed to resolve the contradiction between rapidity and overshoot. Based on the established mathematical model of single-axis drive, a self-disturbance rejection + PD dual closed-loop control structure is adopted; subsequently, a deviation self-coupling PID compensation strategy is proposed for the synchronization issue of bilateral drive in one direction. Experimental results demonstrate that the control strategy proposed in this paper has short response time, good disturbance rejection, and high tracking accuracy.