Food-derived antidiabetic peptides regulate glucose and insulin sensitivity through a novel multi-tier gut-immune-metabolic framework

Type 2 diabetes mellitus (T2DM), characterized by impaired glucose homeostasis and chronic hyperglycemia, remains a significant global health challenge. Current pharmacological interventions, such as synthetic dipeptidyl peptidase-IV (DPP4) inhibitors, improve glycemic control but often carry safety concerns and may not address the multifaceted pathology of the disease comprehensively. This creates a critical need for safer, more accessible, and pleiotropic therapeutic alternatives. Food-derived bioactive peptides have emerged as a promising area of research due to their inherent safety, wide availability, and ability to exert multi-target activities, offering a natural approach to diabetes nutritional intervention. This review addresses the gap by proposing a holistic systems biology framework to understand their complex regulatory roles.