Buffalo milk is highly appreciated for its nutritive properties and highly employed in dairy products, despite this the release of bioactive peptides has not been investigated thoroughly. The aim of this work was to characterize in detail the bioaccesible peptides from buffalo-milk dairy products. Six products were subjected to in vitro simulated gastrointestinal digestion and then analyzed by LC-HRMS. The identified peptides were 165 in Yoghurt, 152 in Scamorza, 146 in Mozzarella, 136 in Grana and Ricotta, 120 in Ice Cream samples, belonging to both buffalo caseins (αs1-, β-, k-CN) and whey proteins (α-LA, β-LG). The identified peptide sequences were subjected to a database driven bioactivity search. Results highlighted a wide range of potential bioactive peptides, including antihypertensive, immunomodulatory, antimicrobial, antidiabetic, anticancer and antioxidant activity. These data evidence the content of healthy peptides released from buffalo-milk dairy products and suggest that the specific technological process influence their bioaccessibility. •Peptidomic profile of six buffalo-milk dairy products was investigated.•In vitro simulated gastrointestinal digestion was carried out.•Bioaccessibility of peptides was assessed by LC-HRMS experiments.•Database-driven specific bioactivity assessment was performed.•A large number of bioactive peptides depending on the manufacturing process were identified.