This study aimed to evaluate the bio‐accessibility of the phenolics and flavonoid, the polyphenolic profile and the antioxidant activity of sprouts obtained from four different quinoa genotypes and one djulis cultivar during in vitro gastrointestinal digestion. Compared to their content in sprouts, the bioavailable phenolics after the oral phase, the gastric phase, the intestinal phase, and in the dialyzable fraction were in the ranges of 45.7%–63.5%, 87.6%–116.7%, 89.6%–124.5%, and 7.4%–10.9%, respectively. The trend in flavonoid bio‐accessibility was similar to the polyphenols. The dialyzable flavonoid recoveries varied between 4.2% and 12.4%. Correspondingly, the free radical scavenging activity of the dialyzable phase decreased significantly from 84.7% to 96.5%. The main phenolic acids were vanillic acid, caffeic acid, and syringic acid during digestion. The results suggest that gastrointestinal digestion greatly affected the absorption of polyphenols and flavonoid of quinoa and djulis sprouts, as well as their antioxidant capacity.