Dipeptidyl peptidase-4 (DPP4) is an integral membrane glycoprotein that modulates the pathological state of diabetes mellitus (DM), and DPP4 inhibitors are a new class of anti-type-2 DM drugs. Recent preclinical studies have associated DPP4 inhibition with improved myocardial systolic and diastolic function. Based on preclinical findings, we investigated associations between the administration of DPP4 inhibitors and cardiac function after acute myocardial infarction (AMI) in a clinical setting. We enrolled 34 patients with diabetes who were treated for acute myocardial infarction at our hospital between January 2010 and December 2012. We retrospectively compared changes in cardiac parameters determined by trans-thoracic echocardiography between patients treated with (DPP4-I group; n = 13) or without (non-DPP4-I group; n = 21) a DPP4 inhibitor during follow-up. The values of E/e′ and of e′/a′ significantly decreased and increased, respectively, in the DPP4-I, compared with the non-DPP4-I group (−2.53 ± 5.53 vs. 2.58 ± 5.68, p = 0.038 and 0.08 ± 0.23 vs. −0.12 ± 0.21, p = 0.036, respectively). We concluded that DPP4 inhibitors could improve E/e′ and e′/a′ in patients with DM and AMI and thus might be effective for treating left ventricular diastolic failure.