Introduction: The aim of this study was to evaluate changes in retinal capillary nonperfusion areas (RCNPA) and the retinal capillary vessel density (RCVD) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) using widefield optical coherence tomography angiography (WFOCTA) in patients with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with intravitreal ranibizumab injection (IRI). Materials and Methods: Twenty-four eyes of 24 patients with DR and DME candidates to a loading dose of IRI were enrolled. All patients underwent WFOCTA with the PLEX Elite 9000 device with 15 × 9 mm scans centered on the foveal center at baseline (T0) and 1 month after each intravitreal injection at 30 days (T1), 60 days (T2), and 90 days (T3). In all patients, the variation of RCNPA and the RCVD of the SCP and DCP were calculated using automatic software written in MATLAB (MathWorks, Natick, MA, USA). Results: The SCP showed a significant longitudinal variation of RCNPA (p = 0.04). Post hoc analysis revealed a statistically significant reduction of RCNPA at T1 (p = 0.04) and a nonsignificant reduction at T2 (p = 0.18) and T3 (p = 0.96). The DCP showed longitudinal changes in the RCNPA that tended to statistical significance (p = 0.09). Post hoc analysis revealed a trend toward a statistically significant reduction of RCNPA at T3 (p = 0.09) not statistically significant at T1 (p = 0.17) and T2 (p = 0.75). The RCVD of SCP and DCP showed no significant changes at any of the time points. Conclusions: WFOCTA showed a decrease in RCNPA after IRI, probably related to the reperfusion of retinal capillaries.