Diabetes mellitus is a global health challenge marked by progressive pancreatic β-cell dysfunction, insulin resistance, and systemic metabolic imbalance. Despite pharmacological advances, current therapies remain largely supportive, failing to halt disease progression or restore endogenous insulin secretion. Biotechnology has transformed the landscape of diabetes research and therapy by enabling precise disease modelling, gene and cell-based interventions, and real-time metabolic monitoring. Tools such as CRISPR-Cas9, TALENs, and Cre-lox systems allow for tissue- and time-specific gene manipulation to investigate pathophysiological mechanisms and develop targeted therapies. Gene therapies and antisense oligonucleotides targeting insulin signalling, glucose metabolism, and inflammatory pathways show promise in preclinical and clinical studies for both type 1 and type 2 diabetes. Simultaneously, advances in stem cell biology and 3D bioprinting have enabled the differentiation, maturation, and encapsulation of insulin-producing β-cells from induced pluripotent stem cells (iPSCs), opening pathways for personalized regenerative treatments. Complementing these biological innovations, biosensors, smart insulin pumps, and closed-loop artificial pancreas systems exemplify the integration of engineering with therapeutic strategies. This chapter synthesizes recent biotechnological advances and explores how artificial intelligence, machine learning, and data-driven precision medicine may soon redefine diabetes management—transforming it from chronic disease care to curative intervention.