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Here, we present a first\u2010in\u2010class microneedle system that redefines eugenol (EUG), a natural compound, as a multifunctional self\u2010assembling material. Beyond its intrinsic therapeutic activity, EUG autonomously forms nanoscale assemblies that penetrate biofilms, suppress inflammation, and act as a natural penetration enhancer. Leveraging these properties, we designed a spatiotemporally controlled microneedle platform integrating dual\u2010phase EUG self\u2010assembly with puerarin (PUE) co\u2010delivery. At the wound surface, EUG assemblies disrupt biofilms and alleviate early inflammation; in deep tissues, their progressive self\u2010assembly sustains antibacterial and anti\u2010inflammatory activity. Meanwhile, EUG facilitates PUE diffusion, while its interaction with the chitosan\u2010based porous matrix ensures gradual release to promote angiogenesis, collagen remodeling, and structured tissue regeneration. Importantly, biodegradable tips detach within 1\u00a0h, minimizing secondary trauma. In an infected diabetic rat model, this system halved bacterial burden, reduced interleukin\u20106 by 60%, accelerated wound closure by 35%, doubled cluster of differentiation 31 expression, and achieved 96.6% \u00b1 4.3% collagen deposition within 14 days, significantly outperforming a commercial silver dressing. This multifunctional, surfactant\u2010free biomaterial platform offers a safe and translational strategy to overcome the \u201cinfection\u2010inflammation\u2010healing barrier\u201d in chronic DFUs.<\/jats:p>","DOI":"10.1002\/smll.74941","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:23:32Z","timestamp":1785493412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatiotemporally Controlled Double Self\u2010Emulsifying Microneedles for Co\u2010Delivery of Eugenol and Puerarin to Promote Healing and Tissue Regeneration of Infected Diabetic Wounds"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3644-8988","authenticated-orcid":false,"given":"Peiya","family":"Shen","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Pharmacy China Pharmaceutical University  Nanjing People's Republic of 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