Atopic dermatitis is a chronic inflammatory skin condition that typically manifests in infancy and is characterized by dry, irritated skin. Here, we propose a self-powered hydration-monitoring and drug-delivery skin patch for closed-loop treatment of atopic dermatitis. The patch is composed of piezoelectric generator, hydration sensing unit, microneedle treatment module and flexible circuit. The piezoelectric PZT generator can achieve self-powering by harvesting mechanical energy from patient activities, allowing for long-term work of the system without external power sources. The hydration sensing unit can rapidly and accurately detect changes in skin hydration by estimating the thermal conductivity. Upon detecting abnormal skin hydration levels for 65 s, the treatment module is automatically activated, heating hyaluronic acid-based microneedles (~42 °C) to release dexamethasone sodium phosphate (DEX), thereby providing timely targeted therapy and moisturization to the affected area within minutes. Therapeutic results in mice model of atopic dermatitis demonstrate that our patch can effectively treat this skin disease, improving the epidermal thickness, IL-4, spleen size and mass. The system achieves closed-loop detection and treatment of atopic dermatitis without external intervention, offering a novel approach to managing skin disease and expanding the scope of self-powered biomedical engineering systems. A self-powered hydration-monitoring and drug-delivery skin patch is designed for closed-loop treatment of atopic dermatitis. The patch composes of piezoelectric generator, hydration sensing unit, microneedle treatment module, and flexible circuit. This integrated system achieves closed-loop detection and treatment of atopic dermatitis without external intervention, offering a novel approach to managing skin disease and expanding the scope of self-powered biomedical engineering systems.© 2025. The Author(s).