Objective: To compare the efficacy and safety of intravitreal dexamethasone implant (IDI) and ranibizumab for the treatment of diabetic macular edema (DME). Methods: PubMed, the Cochrane Library, Embase, Web of Science, Wanfang data, CNKI, and VIP Database were comprehensively searched for studies comparing dexamethasone implant versus ranibizumab in patients with DME. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and adverse events were extracted from the final eligible studies. RevMan 5.3 software was used for data analysis. Random and fixed effect models were applied to evaluate heterogeneity and publication bias. Results: A total of 5 studies involving 593 patients were included in the Meta-analysis. The IDI group had a greater CMT reduction than the ranibizumab group at 1 month after treatment [weighted mean difference (WMD) =−107.13; 95% confidence interval (CI): −149.44 to −64.81; P<0.00001]. At 3 months after treatment, there was a significantly statistical difference in macular edema (ME) between the two groups (WMD =−58.10; 95% CI: −88.39~−27.82; P=0.0002). However, no significant difference in BCVA was found between the two groups either at 1 month (WMD =−0.08; 95%CI: −0.23 to 0.07; P=0.28) or 3 months (WMD =−0.09, 95%CI: −0.09 to 0.01; P=0.08) after treatment. The IDI group faced a higher risk of cataract (OR=4.23, 95%CI: 1.93 to 9.26; P=0.0003) and intraocular pressure (IOP) elevation (OR=8.55, 95%CI: 4.63 to 15.81; P<0.00001) than the ranibizumab group with fewer injections. Conclusion: Both IDI and ranibizumab can improve BCVA and reduce CMT. Compared with ranibizumab, IDI had no difference in improving BCVA, showed better efficacy in reducing ME with fewer injections, yet more side effects.