Reactive oxygen species (ROS) have a versatile function in cellular physiology and pathology, functioning as oxidative stress inducers and signaling molecules. In chronic metabolic disorder such obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD), uncontrolled reactive oxygen species (ROS) generation impairs redox balance, triggering low-grade inflammation. This ROS-mediated inflammatory cascade is driven by mitochondrial dysfunction, activation of pro-inflammatory transcription factors, and impaired antioxidant activity. The resulting inflammation exacerbates insulin resistance, lipid accumulation, and endothelial dysfunction, perpetuating metabolic disease progression. Clinically, elevated biomarkers of oxidative stress and inflammation correlate with disease severity and complications. Therapeutic strategies targeting ROS, including antioxidants, lifestyle interventions, and pharmacologic agents, are under investigation to modulate inflammatory responses and improve metabolic outcomes. This chapter explores the clinical and preclinical implications and emerging interventions focused on ROS-mediated inflammation in metabolic disorders.