Plant-derived extracellular vesicles are functional nanovesicles that have significant applications in both disease prevention and treatment, as well as for use as drug carriers. Momordica charantia is a widely consumed food that has both medicinal and nutritional properties and has shown intervention in diabetes and inflammation caused by oxidative damage. In this study, Momordica charantia-derived extracellular vesicles (MCEVs) were extracted and demonstrated to have excellent antioxidant activity by characterization, lipid composition analysis, protein domain analysis, and in vitro antioxidant measurement. In addition, in vivo studies indicated that the MCEVs could restore ulcerative colitis by regulating oxidation and inflammatory factors. Therefore, the antioxidant properties of MCEVs may be important in protecting the colon from inflammation, which provides new insights into the application of MCEVs as drugs or vectors for intervention in ulcerative colitis.