Based on the background of atomic force microscope (AFM) driven by piezoelectric actuators (PEAs), this paper proposes a sliding mode control coupled with an inverse Bouc-Wen (BW) hysteresis compensator to improve the positioning performance of PEAs. The intrinsic hysteresis and creep characteristics degrade the performance of the PEA and cause accuracy loss. Although creep effect can be eliminated by the closed-loop control approach, hysteresis effects need to be compensated and alleviated by hysteresis compensators. For the purpose of dealing with the estimation errors, unmodeled vibration, and disturbances, a sliding mode control with perturbation estimation (SMCPE) method is adopted to enhance the performance and robustness of the system. In order to validate the feasibility and performance of the proposed method, experimental studies are carried out, and the results show that the proposed controller performs better than a proportional-integral-derivative (PID) controller at 1 and 2 Hz, reducing error to 1.2% and 1.4%, respectively.