<p>Glycogen is not only a critical energy storage molecule in oyster but also a key flavor-determining factor that affect their fatness, with glycogen content directly governing oyster quality. However, the molecular mechanisms underlying glycogen storage and metabolism in shellfish (including oyster) remain incompletely understood. In order to clarify the regulatory mechanisms of glycogen metabolism in Jinjiang oyster (<i>C. ariakensis)</i>, we performed integrated transcriptomic and proteomic analyses on the mantle tissues with high glycogen content (HG) and low glycogen content (LG). The results identified 899 differentially expressed genes (DEGs) at the transcriptional level and 1294 differentially expressed proteins (DEPs) at the translational level, respectively. Functional enrichment analysis demonstrated that these DEGs and DEPs were mainly enriched in glycogen metabolism and energy metabolism-related pathways, including the insulin signaling pathway, starch and sucrose metabolism, and glycerolipid metabolism. In the HG, numerous key genes and proteins were significantly involved in glycogen synthesis, gluconeogenesis, glycolysis pathways and fatty acid metabolism were significantly upregulated. These findings indicate these multiple metabolic processes co-regulate the level of glycogen in the mantle, providing a theoretical basis for elucidating molecular mechanisms of glycogen metabolism and valuable insights for the breeding of high-glycogen oyster varieties.</p>