Fennel (Foeniculum vulgare Mill.) waste contains a broad range of bioactive molecules, including polyphenols, which have poor bioaccessibility during gastrointestinal digestion. This work aimed to investigate the bioaccessibility of total phenolic compounds and the antioxidant capacity during simulated gastrointestinal digestion using two nutraceutical formulations based on non-acid-resistant (NAR) and acid-resistant (AR) capsules containing aqueous-based extracts from fennel waste. Moreover, to obtain a comprehensive investigation of the polyphenolic constituents of the fennel waste extract, a high-resolution mass spectrometry (Q-Orbitrap) analysis was performed. Notably, chlorogenic acids, such as 4-caffeoylquinic acid and 3,4-dicaffeoylquinic acid, were the most detected compounds found in assayed samples (1.949 and 0.490 mg/g, respectively). After in vitro gastrointestinal digestion, the extract contained in AR capsules displayed higher bioaccessibility in both the duodenal and colonic stages (1.96 and 5.19 mg GAE/g, respectively) than NAR capsules (1.72 and 3.50 mg GAE/g, respectively), suggesting that the acidic gastric conditions negatively affected the polyphenol compounds released from the NAR capsules. Therefore, the aqueous extract of fennel waste could be proposed as an innovative and easily available source of dietary polyphenols. Furthermore, the use of an AR capsule could improve the polyphenol bioaccessibility and can be proposed as a nutraceutical formulation.