Metabolic diseases encompass a range of disorders characterized by abnormal metabolism, including obesity, diabetes mellitus, alcoholic/nonalcoholic fatty liver disease, and their associated hyperlipidemia. In recent years, there have been discoveries regarding changes in the genetics and functions of the endocrine system in these metabolic disorders. Extensive research has focused on nicotinamide coenzyme and its relationship to metabolic diseases. Mitochondria, NADPH oxidases, and xanthine oxidases have all been identified as potential contributors to ROS production. Nicotinamide coenzymes I (NAD+/NADH) and II (NADP+/NADPH) are crucially involved in various synthetic metabolic pathways such as lipid synthesis, cholesterol synthesis, and fatty acid chain elongation. This article reviews the signal pathways closely related to nicotinamide coenzymes participating in the occurrence and treatment of alcoholic fatty liver disease, diabetes, and its complications. It also discusses the potential therapeutic applications of coenzymes for these diseases.