Currently there is lack of data regarding the use of optical coherence tomography (OCT) to depict the hemodynamic relevance of coronary stenoses in diabetic patients. We sought to assess the diagnostic accuracy of OCT-derived morphologic assessment in identifying hemodynamically significant coronary lesions as determined by both, the resting instantaneous wave-free ratio (iFR) and the hyperemic fractional flow reserve (FFR) in diabetic patients. Diabetic patients presenting with at least one intermediate coronary lesion were prospectively and consecutively enrolled. All lesions were systematically assessed by iFR, FFR and OCT. A total of 41 intermediate lesions were analysed. Mean iFR and FFR values were 0.90 ± 0.04 and 0.81 ± 0.06, respectively (intra-class correlation coefficient 0.49; 95% CI 0.22-0.79). A moderate correlation between iFR and OCT derived minimal lumen diameter (MLD, r = 0.49) and minimal lumen area (MLA, r = 0.50) was found. Conversely, there was a poor correlation between FFR and OCT-derived MLD (r = 0.34) and MLA (r = 0.32). The diagnostic efficiency of MLA and MLD to identify iFR significant stenoses showed an AUC of 0.82 (95% CI 0.69-0.95) for MLD and 0.83 (95% CI 0.71-0.96) for MLA. A worse diagnostic efficiency was found when FFR was used as the reference with an AUC of 0.71 (95% CI 0.54-0.87) for MLD and 0.70 (95% CI 0.53-0.87). OCT-derived MLA and MLD were the strongest independent anatomic predictors of abnormal iFR and FFR values. In diabetic patients, OCT-derived MLA and MLD showed a moderate diagnostic efficiency in identifying functionally significant coronary stenoses by FFR or iFR. In diabetics, anatomic OCT measurements better predicted resting than FFR-determined physiologically significant lesions.