Human breast milk harbors commensal lactic acid bacteria with probiotic potential, and microbial fermentation may enhance the bioactivity of plant-derived exosome-likenanovesi cles (EVs); this study evaluated whether L. plantarum BMSE-HMP251 isolated from breast milk could safely ferment Hordeum vulgare L. and improve the anti-inflammatory activity of derived EVs. BMSE-HMP251 was identified by 16S rRNA sequencing and characterized by biochemical, safety, and genomic analyses. EVs derived from Hordeum vulgare L. extract and BMSE-HMP251-fermented broth were evaluated for physicochemical properties, an tioxidant activity, cytotoxicity, and anti-inflammatory activity in LPS-stimulated HT-29 and RAW 264.7 cells. EVs derived from Hordeum vulgare L. fermentation exhibited a distinct size distribution and significantly enhanced bioactivity, including higher DPPH radical scavenging activity and greater suppression of nitric oxide production and proinflamma tory cytokine (TNF-α and IL-1β) mRNA expression, compared with EVs from unfermented extracts. These effects were observed following fermentation with the human breast milk derived strain L. plantarum BMSE-HMP251, which showed species-consistent phenotypic and genomic characteristics and no safety concerns. Overall, fermentation markedly en hances the anti-inflammatory potential of plant-derived EVs, supporting fermentation as a safe and effective strategy to improve their functional value. Keywords: fermentation; Lactiplantibacillus plantarum BMSE-HMP251; exosome-like nanovesicles; Hordeum vulgare L. anti-inflammatory activity