Diabetes, a multifactorial metabolic disorder, is characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Increasing evidence suggests that oxidative stress and inflammation play central roles in the onset and progression of both diabetes. Reactive oxygen species (ROS), generated endogenously through mitochondrial dysfunction, Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase activation, and other enzymatic sources, disrupt cellular redox balance and contribute to pancreatic β-cell dysfunction, impaired insulin signaling, and systemic complications. In parallel, chronic low-grade inflammation is a hallmark of diabetes, mediated by pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and IL-1β. These cytokines activate key inflammatory signaling pathways including nuclear factor-kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and the Nucleotide-binding domain, leucine-rich containing family, pyrin domain-containing-3 (NLRP3) inflammasome. Notably, ROS act as upstream activators of these pathways, establishing a vicious cycle between oxidative stress and inflammation. This crosstalk aggravates insulin resistance, enhances β-cell apoptosis, and accelerates vascular and neural damage. Understanding the molecular interplay between ROS and inflammatory mediators provides critical insights into the pathogenesis of diabetes and its complications, including nephropathy, neuropathy, retinopathy, and cardiovascular disease. Therapeutically, targeting this ROS-inflammation axis offers promising strategies for intervention. The use of antioxidants, anti-inflammatory agents, and natural compounds has shown potential in mitigating these pathways, although challenges remain in clinical translation. This chapter aims to elucidate the dynamic interconnection between oxidative stress and inflammation in diabetes, highlight key molecular mechanisms involved, and explore emerging therapeutic approaches that could disrupt this deleterious cycle to improve patient outcomes.