This paper presents a new fractional-order sliding mode controller (FOSMC) for disturbance rejection and stabilization of a class of fractional-order systems with mismatched disturbances. To design this control strategy, firstly, a fractional-order extended disturbance observer (FOEDO) is proposed to estimate the matched and mismatched disturbances and their derivatives. Then, according to the design procedure of the sliding mode controller and based on the designed FOEDO, a proper sliding mode surface is proposed. Subsequently, the proposed FOSMC is designed to guarantee that the system states reach the sliding surface and stay on it forever. The stability of the controlled fractional-order systems is proved via fractional-order Lyapunov stability theory. The numerical examples are used to illustrate the effectiveness of the proposed fractional-order controller. The simulation results of the proposed FOSMC are compared with the results of some other researchers’ works to show the superiority of the proposed control method. The new approach displays some attractive features such as fast response, the chattering reduction, robust stability, less disturbance estimation error, the mismatched disturbance, noise rejection, and better control performance.