According to the results of the active components and key gene-pathway interaction network, the antihyperglycemic effect of Diospyros lotus L is attributed to quercetin, luteolin, kaempferol, myricetin, and dihydromyricetin, which act on PTGS2, AKT1, IL6, TNF, and MMP9 and participate in the TNF, PI3K-Akt, and HIF-1 signaling pathways, as well as NAFLD. Here, PTGS2 is linked to metabolic dysfunction-associated steatotic liver disease.