SummaryIn the current study, polyphenols were extracted from chestnut (Castanea sativa) shells (CSS) by two eco‐friendly techniques, namely microwave‐assisted extraction (MAE) and ultrasound‐assisted extraction (UAE). The bioaccessibility, phenolic composition and bioactivity of CSS extracts were explored upon in vitro gastrointestinal digestion considering a future nutraceutical use. The phenolic and flavonoid concentrations, bioaccessibility and antioxidant/antiradical properties of both extracts decreased during digestion. The bioaccessibility was 25% and 26%, respectively, for UAE and MAE extracts. The phenolic profile demonstrated that gallic acid, caftaric acid and catechin were the most bioaccessible compounds for both extraction techniques. The CSS extracts unveiled notable radicals scavenging efficiency, particularly against HOCl (18.32–75.44% inhibition) and ONOO− (16.78–86.11% inhibition), as well as hypoglycaemic (6.95–17.99% α‐amylase inhibition) and neuroprotective (16.44–54.66% AChE inhibition) properties upon digestion. Considering the undigested extracts, the UAE extract revealed better results than the MAE extract. Oppositely, among digested fractions the MAE digests disclosed the most promising outcomes. The remarkable contribution of phenolic compounds to the bioactivity of CSS extracts after in vitro digestion was proved by heatmap correlations, indicating that their pro‐healthy properties were modified after gastrointestinal digestion, being ascribed to the distinct phenolic composition. This study evaluates, for the first time, the impact of in vitro gastrointestinal digestion on the bioaccessibility and bioactivity of phenolics‐rich CSS extracts prepared by UAE and MAE.