The gut microbiota has been recognised as a key modulator of metabolic health, affecting glucose homeostasis, insulin sensitivity, and inflammation. Alterations in gut microbial community, or dysbiosis, have been implicated in the onset and progression of type 2 diabetes mellitus (T2DM). Emerging evidence also implicates gut microbiota imbalance in colorectal cancer (CRC) with a common pathogenic pathway through chronic inflammation, dysregulated immune responses, and metabolic endotoxemia. Therapeutic interventions of the gut microbiota, such as the administration of probiotics, prebiotics, synbiotics, and dietary changes in diabetes and CRC, provide promising strategies for individualised interventions that may enhance metabolic and oncologic benefits. The knowledge of these interconnected strategies provides new avenues for the prevention and management of diabetes and CRC. This chapter explores the intricate relationships between gut microbiota and glucose metabolism, while it also discusses the effects of dietary and lifestyle interventions, and assesses the contribution of microbiota-derived metabolites to diabetes pathophysiology. In addition, it also highlights the new evidence linking diabetes and CRC through dysregulation of gut microbes.