BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disorder marked by persistent inflammation and damage to the intestinal mucosa. Despite significant advances in treatment, there remains an unmet need for more effective and safer therapeutic strategies. RESULTS: In this study, we isolated and characterized extracellular vesicle-like nanoparticles (ELNs) derived from Coptis chinensis (Cc-ELNs) and evaluated their therapeutic potential in IBD. Intraperitoneal administration of Cc-ELNs in dextran sulfate sodium (DSS)-induced colitis mice demonstrated selective targeting of inflamed intestinal regions. Cc-ELNs significantly alleviated colitis by reducing neutrophil recruitment and inhibiting the formation of neutrophil extracellular traps (NETs). Furthermore, by suppressing NET formation, Cc-ELNs mitigated pyroptosis in intestinal epithelial cells (IECs) and promoted the proliferation of both IECs and intestinal stem cells (ISCs). Mechanistically, Cc-ELNs delivered miR-5106, which downregulated Slc39a2 expression, thereby restoring zinc homeostasis in neutrophils and reducing NET formation. CONCLUSIONS: These findings establish Cc-ELNs as a novel, natural, and effective therapeutic candidate for IBD, highlighting the potential of plant-derived nanoparticle-based therapies.