7-O-Galloyl-D-sedoheptulose (GS) is the bioactive polyphenol isolated from the low-molecular-weight fraction of Corni Fructus (Cornus officinalis Sieb. et Zucc.). The present study was conducted to examine whether GS has an ameliorative effect on the liver of type 2 diabetic db/db mice. GS (20 or 100 mg/kg body weight/day, per os) was administered every day for 6 weeks to db/db mice, and its effect was compared with vehicle-treated db/db and m/m mice. The administration of GS decreased the elevated serum glucose, leptin, insulin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), resistin, and hepatic functional parameters, and reduced the increased fluorescent advanced glycation endproducts (AGEs) and reactive oxygen species in the liver. The db/db mice exhibited the up-regulation of receptor for AGEs (RAGE) and AGE-related proteins; however, GS treatment significantly reduced those expressions. Moreover, the augmented expressions of oxidative stress- and inflammation-related proteins, phospho-extracellular-signal regulated kinase 1/2, phospho-c-Jun N-terminal kinase, nuclear factor-kappa B, activator protein-1, monocyte chemotactic protein-1, intracellular adhesion molecule-1, TNF-α, and IL-6, were down-regulated by GS administration. Hematoxylin-eosin staining showed that the increased hepatocellular damage in the liver of db/db mice improved with GS administration. The present results support the evidence for GS ameliorating hepatic damage through the RAGE-mediated inflammation pathway.