Background: Type 2 Diabetes Mellitus (T2DM) represents a growing global health crisis, with profound implications for public health systems worldwide. The interplay between nutritional factors and biochemical pathways in T2DM pathogenesis and management remains incompletely characterized.

Objective: This systematic review aims to synthesize current evidence on the nutritional and biochemical mechanisms underlying T2DM development and the efficacy of dietary interventions in disease management.

Methods: We conducted a systematic literature search following PRISMA 2020 guidelines across PubMed, Scopus, Web of Science, and Google Scholar from inception to October 2024. Studies investigating nutritional biomarkers, dietary patterns, biochemical pathways, and metabolic interventions in T2DM were included.

Results: Eighty-three studies met the inclusion criteria. Analysis revealed strong evidence for insulin resistance mechanisms involving AMPK and PPAR-γ pathways, gut microbiome modulation of glucose metabolism, and the role of advanced glycation end-products (AGEs) in complications. Mediterranean and low-carbohydrate diets demonstrated significant HbA1c reductions (0.5-1.5%), while specific micronutrients (magnesium, chromium, vitamin D) showed modest glycemic benefits.

Conclusion: T2DM management requires integrated nutritional and biochemical approaches targeting multiple pathological pathways. Personalized nutrition based on biochemical profiling represents a promising frontier for precision medicine in diabetes care.