Abstract: Objective: To explore the composition of limon peel polyphenols (LPP) and its influence on glucose metabolism in insulin resistance (IR) HepG2 cells. Methods: The composition of LPP was analyzed by HPLC-QTOF-MS. HepG2 cells were used to establish insulin resistance model, IR-HepG2 cells were treated with LPP, and the effect of LPP on glucose metabolism was preliminarily investigated by measuring glucose consumption. By determining glycogen content and hexokinase (HK), pyruvate kinase (PK), phosphoenol pyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) activities to explore the pathway of LPP regulating glucose metabolism in cells. Results: Twelve compounds were identified by HPLC-QTOF-MS, mainly flavonoids and their glycosides. In the study of glucose metabolism, compared with the model group, the concentration of 0.1~2 mg/mL lemon peel polyphenols significantly increased glucose consumption (P<0.05), and the ability to increase the glycogen content and HK and PK activities and decrease the PEPCK and G6Pase activity of IR-HepG2 cells was closest to metformin-positive control when the concentration of lemon peel polyphenols was 0.5 mg/mL. Conclusion: Lemon peel polyphenols can reduce IR-HepG2 cell state of insulin resistance, and can promote glycogen synthesis, improve the glycolytic key enzyme activity, reduce sugar dysplasia regulate sugar metabolism enzyme activity way, it provides data support for the subsequent research in the body, and provides the theoretical basis for the future development of functional products.