•Germinated amaranth (GA) was subjected to in vitro simulated gastrointestinal digestion.•GA peptides were released after gastrointestinal digestion.•GA digests and peptides showed anti-inflammatory effect.•GA peptides fraction (3–10 kDa) exhibited higher antioxidant activity.•Antioxidant and anti-inflammatory peptides sequences in GA digests were identified. Amaranth (Amaranthus hypochondriacus) is an ancestral nutritional grain and good source of bioactive compounds as peptides. In this study, the effect of in vitro simulated gastrointestinal digestion (SGD) of germinated amaranth on the release of antioxidant and anti-inflammatory peptides was evaluated. The germinated amaranth peptides generated during SGD were released after 90 min of incubation with pancreatin and fractioned to F1 (>10 kDa), F2 (3–10 kDa), and F3 (<3 kDa). Among germinated amaranth peptides fractions tested, F2 had the highest antioxidant activity, while F1 and F2 exhibited a high anti-inflammatory response caused by lipopolysaccharide-induced in RAW 264.7 macrophages. A total of 11 peptides sequences were identified in the fractions evaluated, and they exhibit potential biological activity against non-communicable diseases. The findings from this study showed first time report on bioactive peptides, especially anti-inflammatory, from germinated amaranth released by in vitro gastrointestinal digestion.