Abstract Background Some studies have suggested that blood glucose fluctuation and C-peptide level were considered as predictive factors for carotid artery intima–media thickness (CIMT). However, the relationships of these variables are unclear. This research was aimed to identify the potential effects of blood glucose fluctuation, C-peptide level and conventional risk factors on CIMT. Methods A total of 280 type 2 diabetes mellitus (T2DM) patients were enrolled into this study. Population characteristics were obtained through medical history and clinical parameters. The patients were divided into two groups according to the critical value of CIMT (0.9). Research data were analyzed to identify risk factors of CIMT between the two groups. Results The comparison results of basic information showed that differences in age and illness years between the two groups were statistically significant (p = 0.0002 and p = 0.0063). Logistic regression analysis results indicated that smoking, uric acid (UA) levels, 2 h C-peptide and standard deviation of blood glucose (SDBG) were the influence factors for CIMT thickening (p = 0.032, p = 0.047, p = 0.049 and p = 0.042, respectively). Blood glucose fluctuation could affect the risk of some complications. In largest amplitude of glycemic excursions (LAGE) > 4.4 group, the CIMT abnormal rate was 27.10%, which was significantly higher than 12.12% in the LAGE ≤ 4.4 group (p = 0.012). The CIMT abnormal rate of SDBG > 2.0 group was 27.81%, which was significantly higher than that of the SDBG ≤ 2.0 group (p = 0.018). Conclusions Blood glucose fluctuation is an independent risk factor associated with CIMT in T2DM patients, in addition to conventional risk factors, such as smoking, high UA level and 2 h C-peptide. Therefore, more attention should be given to the change of CIMT and the complications.