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Diabetes Mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia resulting from the body's inability to produce insulin or effectively respond to it. In this review, we summarize the cellular and molecular mechanisms involved in common clinical manifestations of DM, including neuropathy, retinopathy, nephropathy, sensorineural hearing loss, cardiovascular disease, stroke, immune dysfunction, and chronic wounds. Common pathways explored in these dysfunctions include the polyol pathway, formation of advanced glycation end products (AGEs) and their interaction with the receptor for advanced glycation end products (RAGE), mitochondrial dysfunctions leading to overproduction of reactive oxygen species (ROS), and the chronic state of inflammation and inflammatory cytokines. Furthermore, we explore current and developing treatments for DM, along with more targeted therapies for the clinical manifestations of DM. In summary, this review gives a comprehensive overview of the pathways involved in the clinical manifestations of DM, and how these pathways are targets for therapeutics and treatments.