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[Display omitted] Atopic dermatitis (AD) commonly manifests in skin areas subjected to flexion, particularly joints. This underscores the importance of dissolving microneedles (DMNs) used in AD treatment having strong skin adhesion to prevent drug delivery interruption due to patch detachment during patient activity. Moreover, matrine (MAT), a prominent active ingredient derived from the natural plant Sophora flavescens, is known for its significant efficacy in treating skin inflammation, itching, and allergic diseases. Herein, we presented MAT-loaded DMNs (MAT-DMNs) specifically tailored for joint skin application in AD treatment. MAT-DMNs can rapidly dissolve and hydrate after application, demonstrating adhesive properties on ex vivo pig skin, rat abdominal skin, and finger joint skin, thereby ensuring sustained and uninterrupted drug delivery to the skin. In vitro evaluations revealed that MAT-DMNs exhibited 24-hour first-order release profiles with cumulative penetration rates of 78.70 ± 4.24 % and 77.14 ± 6.65 % for the low-dose and high-dose groups, respectively. Furthermore, these DMNs showed excellent skin compatibility and therapeutic efficacy in AD mice models. Specifically, the skin lesion score in MAT-DMNs group was significantly lower (2.67 ± 0.40) compared to the model group (11.60 ± 1.62) and the blank DMNs group (10.80 ± 1.67). MAT-DMNs effectively alleviated AD symptoms such as itching and inflammation by reducing epidermal thickening, decreasing mast cell infiltration, and lowering the expression of Th2 cytokines (IL-4 and IL-10) and pro-inflammatory factors (IL-1β, IL-6, and TNF-α) compared to the blank DMNs group (p < 0.01). These findings suggest that MAT-DMNs hold promise for clinical AD treatment, particularly for skin diseases commonly affecting joint areas. [ABSTRACT FROM AUTHOR]