Traditional topical ointment applied on the skin surface has poor drug penetration due to the thickening of the stratum corneum for psoriasis. Microneedles (MNs) provide a desirable opportunity to promote drug penetration. However, the common MNs are difficult to meet the requirement of on‐demand drug delivery. In this study, a smart electrical responsive MNs is fabricated by introducing conductive material of polypyrrole (PPy). Further, a self‐powered controllable transdermal drug delivery system (sc‐TDDS) based on piezoelectric nanogenerator (PENG) is developed. The sc‐TDDS can control drug release by collecting and converting mechanical energy into electrical energy. The sc‐TDDS can release 8.5 ng dexamethasone (Dex) subcutaneously per electrical stimulation. When treating psoriasis‐like skin disease with sc‐TDDS, the inflammatory skin returned to normal after 5 days, which is obviously better than treating with traditional Dex solution coating. This work provides a promising approach of on‐demand transdermal drug release for various disease treatment scenarios.

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