Objective To investigate the regulation effect of silybin in the treatment of newly diagnosed type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) on the progression of liver fibrosis and the disorder of glucose and lipid metabolism. Methods 93 newly diagnosed T2DM patients with NAFLD admitted to our hospital were selected as the study subjects. They were randomly divided into an observation group of 47 cases and a control group of 46 cases using a random number table. Both groups of patients received exercise, dietary intervention, and metformin treatment, while the observation group received silybin treatment simultaneously. Compare the fasting blood glucose (FPG), 2-hour postprandial blood glucose (2 h PG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), total cholesterol (TC), triglycerides (TG), adiponectin, leptin, interleukin-6 (IL-6), superoxide dismutase (SOD), type III procollagen peptide (III-PC), lamin (LN), hyaluronic acid (HA), liver ultrasound scores, and adverse reactions between two groups before and after treatment. Results After treatment, the FPG, 2 h PG, HbA1c, and HOMA-IR measurements of both groups of patients decreased compared to before treatment (P＜0.05). Before treatment, there was no statistically significant difference in TC, TG, adiponectin, leptin, IL-6, SOD, ultrasound scores, III-PC, LN, and HA measurements between the observation group and the control group (P＞0.05). After treatment, the TC, TG, leptin, IL-6, ultrasound score, III-PC, LN, HA of the observation group were lower than those of the control group (P＜0.05), while the levels of adiponectin and SOD were higher than those of the control group (P＜0.05). ConclusionIn T2DM patients with NAFLD, the treatment of silybin combined with exercise, dietary intervention and metformin can also inhibit the progression of liver fibrosis and regulate the disorder of glucose and lipid metabolism on the basis of good control of blood sugar,the clinical effect is worthy of recognition