<p>Quinoa is a nutritious grain, and its by-product, bran, also contains a variety of active substances. In this study, the effect of extraction with different solvents (water, 50% ethanol, deep eutectic solvents (DESs)) on the polyphenol fractions, antioxidant and lipid-lowering activities and fermentation metabolites of quinoa bran was studied using in vitro digestion. The results showed that the main active compounds of quinoa bran polyphenol extract were flavonoids and cinnamic acid and derivatives, and phenolic acids. Quinoa bran polyphenol extracts using different solvents showed strong antioxidant and lipid-lowering activities, which were enhanced by in vitro digestion of the polyphenol extracts. Metabolomic analysis revealed that DESs and 50% ethanol solvents increased bile acid production by approximately twofold compared to water-extracted polyphenols, while also significantly boosting the generation of dipeptides and polyunsaturated fatty acids. These metabolites protect the intestinal barrier and regulate metabolic-immune homeostasis. DESs solvent can serve as a favorable extraction solvent for quinoa bran polyphenols. This study lays the foundation for the study of functional studies of quinoa bran polyphenols.</p><p></p>