AIM: This retrospective analysis aims to evaluate the correlation between blood glucose fluctuation (BGF) and heart rate variability (HRV) in patients with coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: In total, 210 patients with CHD and T2DM from January 2014 to January 2019 admitted to Wenling Hospital of Traditional Chinese Medicine were enrolled in this study. Based on whether BGF existed, patients were allocated to BG control group and BG fluctuation group. The HRV parameters, frequency of adverse events, and Gensini score between groups were recorded and Pearson analysis was performed. RESULTS: Results displayed that no significant differences in age, gender, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), alcohol consumption history, drinking history, or serum lipid were found between groups (P > 0.05 for all items). However, the BGF parameters were significantly higher while the HRV parameters were significantly lower in BG fluctuation group, compared with BG control group (P < 0.05 for all items). Pearson analysis showed that despite mean blood glucose (MBG) and mean amplitude of glycemic excursions (MAGE) both correlated with a standard deviation of NN intervals (SDNN) level, the correlation coefficient of MAGE-SDNN was much higher (-0.705 vs -0.185). Additionally, the frequencies of adverse events and Gensini scores were also significantly higher in the BG fluctuation group than the BG control group. CONCLUSIONS: It suggests that BGF strongly correlated with HRV in patients with CHD and T2DM. It also provides experimental instructions for clinical practice.