<![CDATA[Graphical Abstract Highlight Research 1. Integrated in silico framework successfully identified antidiabetic peptides from Indonesian shrimp paste (terasi). 2. Shrimp proteins, particularly myosin, actin, and haemocyanin, were predicted as major bioactive peptide precursors. 3. Microbial enzymatic hydrolysis generated peptides with high predicted bioactivity and DPP-IV inhibitory potential. 4. Novel terasi-derived peptides showed favorable safety profiles and stable interactions with the DPP-IV receptor. 5. This study provides molecular insights into fermented seafood as a source of functional antidiabetic ingredients. Abstract The increasing prevalence of Type 2 Diabetes Mellitus has encouraged the exploration of safer therapeutic alternatives, including food-derived bioactive peptides (BAPs) with antidiabetic potential. Indonesian shrimp paste (terasi), a traditional fermented seafood product, is a promising source of BAPs generated through microbial protein hydrolysis. However, systematic identification of antidiabetic peptides from terasi remains limited. This study aimed to predict, identify, and characterize potential antidiabetic BAPs from terasi using an integrated in silico approach, focusing on DPP-IV inhibitory peptides and their molecular interactions. Shrimp-derived protein sequences associated with terasi fermentation were analyzed through an in silico framework. Major protein precursors were subjected to simulated enzymatic hydrolysis using microbial proteases, followed by bioactivity screening, peptide mapping, antidiabetic activity prediction, toxicity and physicochemical assessment, and molecular docking against DPP-IV using AutoDock Vina and GNINA. Myosin, actin, and haemocyanin were identified as major BAP precursors. Microbial enzymatic hydrolysis generated peptides with higher predicted bioactive densities (85.94–89.65%) than non-specific contaminant enzymes (79.05–83.55%). BIOPEP-UWM analysis showed that antidiabetic activity was the dominant predicted function, mainly associated with DPP-IV inhibition (0.269–0.395). Further screening identified promising peptides (VPPHL, PHAIL, ALPPGV, and MAMMAG) with favourable safety profiles, physicochemical properties, and stable interactions within the DPP-IV catalytic pocket. Terasi represents an underexplored source of potential antidiabetic peptides. Further validation through peptide synthesis, in vitro DPP-IV inhibition assays, and biological studies is required to confirm their efficacy and functional food applications.]]>
