Transdermal drug delivery (TDD) systems with feedback control have attracted extensive research and clinical interest owing to their unique advantages of convenience, self-administration, and safety. Here, a self-powered wearable iontophoretic TDD system that can be driven and regulated by the energy harvested from biomechanical motions is proposed for closed-loop motion detection and therapy. A wearable triboelectric nanogenerator (TENG) is used as the motion sensor and energy harvester that can convert biomechanical motions into electricity for iontophoresis without stored-energy power sources, while a hydrogel-based soft patch with side-by-side electrodes is designed to enable noninvasive iontophoretic TDD. Proof-of-concept experiments on pig skin with dyes as model drugs successfully demonstrate the feasibility of the proposed system. This work not only extends the application of TENG in the biomedical field, but may also provide a cost-effective solution for noninvasive, electrically assisted TDD with closed-loop sensing and treatment.