To address the overshoot, oscillation and slow disturbance recovery of the acoustic-pressure envelope in ultrasonic transdermal drug delivery caused by load variation, pure time delay and actuator saturation, an interval type-2 fuzzy self-tuning incremental proportional-integral-derivative (PID) control method considering load uncertainty is proposed. Based on the Butterworth-Van Dyke (BVD) equivalent circuit and envelope baseband modeling, the controlled plant is approximated as a second-order system with pure time delay. Gaussian interval type-2 fuzzy sets, Karnik-Mendel type-reduction and an anti-windup mechanism are introduced to realize bounded online tuning of PID parameters. Simulation results show that, compared with conventional PID, the proposed method reduces root mean square error (RMSE), peak overshoot, settling time and disturbance recovery time by 15.4%, 62.1%, 38.2% and 41.9%, respectively. Compared with type-1 fuzzy PID, interval type-2 fuzzy self-tuning incremental PID (IT2-FPID） further reduces peak overshoot, settling time and disturbance recovery time by 58.6%, 26.8% and 24.7%, respectively. Experimental results show that IT2-FPID outperforms the comparison methods and can achieve fast, stable and robust control for the acoustic-pressure envelope in ultrasonic drug delivery.