Metabolic diseases, including diabetes, obesity, and metabolism-associated fatty liver disease (MAFLD), pose significant health and economic burdens globally. The concept of "metabolic memory" refers to the persistent adverse effects of transient abnormal metabolic states, such as hyperglycemia or hyperlipidemia, even after these conditions are normalized. This phenomenon has been observed in various diseases and complications, highlighting the importance of early and strict control of metabolic disorders. The review traces the history of metabolic memory research, starting with the Diabetes Control and Complications Trial (DCCT) in 1983, which demonstrated that intensive glycemic control significantly reduced the risk of diabetic complications. Subsequent studies, such as the Epidemiology of Diabetes Interventions and Complications (EDIC) and the UK Prospective Diabetes Study (UKPDS), further confirmed the long-term benefits of early and intensive glycemic control. The review discusses the characteristics of metabolic memory, including its persistence, progressivity, and epigenetic regulation. Metabolic memory promotes persistent harmful effects, such as inflammatory changes, premature cell senescence, and apoptosis. These effects are influenced by early control, and subsequent metabolic control does not prevent progressive complications. Epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), play a crucial role in establishing and maintaining metabolic memory. The molecular mechanisms of metabolic memory are explored in detail. DNA methylation, histone modifications, and ncRNAs are key players in this process. DNA methylation, particularly at CpG-rich regions, can suppress gene expression and contribute to the persistence of metabolic memory. Histone modifications, including acetylation, methylation, and phosphorylation, regulate gene transcription and affect cellular metabolism. Non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), also modulate gene expression and play a role in metabolic memory. The review concludes by highlighting the potential of targeting metabolic memory as a therapeutic strategy for metabolic diseases. Understanding the mechanisms of metabolic memory can provide new insights into the pathogenesis of these diseases and offer opportunities for more effective disease detection and management.Metabolic diseases, including diabetes, obesity, and metabolism-associated fatty liver disease (MAFLD), pose significant health and economic burdens globally. The concept of "metabolic memory" refers to the persistent adverse effects of transient abnormal metabolic states, such as hyperglycemia or hyperlipidemia, even after these conditions are normalized. This phenomenon has been observed in various diseases and complications, highlighting the importance of early and strict control of metabolic disorders. The review traces the history of metabolic memory research, starting with the Diabetes Control and Complications Trial (DCCT) in 1983, which demonstrated that intensive glycemic control significantly reduced the risk of diabetic complications. Subsequent studies, such as the Epidemiology of Diabetes Interventions and Complications (EDIC) and the UK Prospective Diabetes Study (UKPDS), further confirmed the long-term benefits of early and intensive glycemic control. The review discusses the characteristics of metabolic memory, including its persistence, progressivity, and epigenetic regulation. Metabolic memory promotes persistent harmful effects, such as inflammatory changes, premature cell senescence, and apoptosis. These effects are influenced by early control, and subsequent metabolic control does not prevent progressive complications. Epigenetic modifications, such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), play a crucial role in establishing and maintaining metabolic memory. The molecular mechanisms of metabolic memory are explored in detail. DNA methylation, histone modifications, and ncRNAs are key players in this process. DNA methylation, particularly at CpG-rich regions, can suppress gene expression and contribute to the persistence of metabolic memory. Histone modifications, including acetylation, methylation, and phosphorylation, regulate gene transcription and affect cellular metabolism. Non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), also modulate gene expression and play a role in metabolic memory. The review concludes by highlighting the potential of targeting metabolic memory as a therapeutic strategy for metabolic diseases. Understanding the mechanisms of metabolic memory can provide new insights into the pathogenesis of these diseases and offer opportunities for more effective disease detection and management.