Background: Patients with type 2 diabetes (T2D) frequently exhibit impaired erythrocyte deformability, which contributes to microvascular dysfunction. We previously reported that imeglimin, a mitochondrial-targeted antidiabetic agent, prolongs erythrocyte lifespan. This study investigated the effects of imeglimin on erythrocyte deformability and its clinical implications in patients with T2D. Methods: This post hoc analysis of the INFINITY study included 25 patients with T2D who completed 6 months of imeglimin treatment (2000 mg/day) followed by a 3-month follow-up. Erythrocyte deformability was evaluated using a microchannel array flow analyzer. Hematological parameters, glycemic markers, and vascular indices, including brachial-ankle pulse wave velocity (baPWV) and toe-brachial index (TBI), were also assessed. Results: Erythrocyte deformability, assessed by 3-month averages, showed an improvement trend at 1–3 months (P = 0.058) and a significant improvement at 4–6 months (P = 0.016) compared with baseline; this effect was reversed after discontinuation. Erythrocyte lifespan significantly increased by 10%–20% during treatment and persisted after discontinuation. Conversely, red blood cell count, hemoglobin, and hematocrit decreased during treatment and recovered post-discontinuation. At 6 months, baPWV increased and TBI decreased, both showing reversibility after treatment cessation. Conclusion: Imeglimin treatment significantly improved erythrocyte deformability in patients with T2D. Although this study did not definitively prove the direct clinical benefits of improved deformability on overall hemorheology or microvascular outcomes, these findings suggest that imeglimin exerts potential pleiotropic effects on circulatory function beyond glycemic control.