Background: Plant-derived extracellular vesicles (PDEV) are emerging as natural nanomedicines for various diseases. Methods: We demonstrated that SEV exert potent antioxidant and anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages and Caco-2 intestinal epithelial cells. Moreover, we assessed the therapeutic effects of SEV on dextran sulfate sodium (DSS)-induced IBD in a murine model. Results: In inflamed RAW264.7, SEV modulated the NF-κB/NLRP3 signaling axis to exert anti-inflammatory effects. They scavenged reactive oxygen species (ROS), restored mitochondrial membrane potential, upregulated the anti-inflammatory cytokine IL-10, and suppressed the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. In Caco-2 intestinal epithelial cells, SEV also repaired intestinal barrier function by restoring expression of the tight junction proteins Zonula Occludens-1 (ZO-1), Claudin-1, and Occludin (OCLN), alongside reduced TNF-α levels. In vivo, SEV accumulated at colonic inflammatory loci to effectively alleviate IBD, as evidenced by improved body weight and increased colon length. This protective effect was mediated through inhibition of the NF-κB/NLRP3 signaling axis in colon tissues, which subsequently restored intestinal barrier integrity by increasing goblet cell numbers, upregulating OCLN proteins, and enhancing Mucin2 (MUC2) secretion, while simultaneously rebalancing inflammatory cytokines through suppression of TNF-α/IL-1β and promotion of IL-10 production. Conclusion: SEV have the potential to protect the colon against DSS-induced colitis by inhibiting the NF-κB/NLRP3 signaling pathway, providing a promising therapeutic candidate for IBD.