Purpose <p>High-intensity interval training therapy (HIIT) has recently emerged as a promising regimen for the management of type 2 diabetic subjects. However, there is no consensus on the best time for HIIT relative to meals. Therefore, this study aimed to investigate the effect of fasted versus post-meal HIIT training on glycemic control in men with type 2 diabetes mellitus (T2DM).</p> Methods <p>This study enrolled 123 subjects suffering from T2DM with ages between 40 and 60 years. Subjects were randomly assigned to one of four groups, the Fasted, Post-breakfast, Post-lunch, and Post-dinner groups practiced HIIT pre-breakfast and 2&#xa0;h after breakfast, lunch, and dinner, respectively. The HIIT program involved three sessions weekly for 12&#xa0;weeks. Glycated hemoglobin (HbA1c), fasting blood glucose, fasting insulin, insulin sensitivity, body composition, and blood lipid values were evaluated pre- and post-intervention.</p> Results <p>The results of the one-way ANOVA analysis revealed a significant improvement in HbA1c levels among the four groups (<i>P</i> &lt; 0.001), with the Post-lunch group having the most notable improvement in HbA1c. Fasting blood glucose, fasting insulin, and HOMA-IR significantly decreased only within the Post-lunch group (<i>p</i> &lt; 0.001). The Fasted group was the only group that showed significant improvement in body composition scores. Ther was no significant changes in blood lipids in response to HIIT in any of the study groups.</p> Conclusions <p>The findings of this study indicate that performing HIIT 2&#xa0;h after lunch may be optimal for enhancing glycemic control, while pre-breakfast HIIT in a fasted state could be the most effective for improving body composition. These findings highlight the importance of synchronizing HIIT with mealtimes to obtain the best benefit from training to improve glycemic control and body composition.</p>