This comprehensive review examines the efficacy, safety, and implications of intravitreal OZURDEX and intravitreal bevacizumab in treating diabetic macular edema (DME). DME is a common complication of diabetes mellitus and a leading cause of vision loss. OZURDEX, through sustained release of dexamethasone, targets inflammation and vascular permeability, while bevacizumab inhibits vascular endothelial growth factor (VEGF), reducing angiogenesis. However, differences in safety profiles exist, with OZURDEX associated with an increased risk of intraocular pressure elevation and cataract formation and bevacizumab potentially carrying systemic risks. The choice between these treatments should be individualized, considering patient preferences, ocular and systemic comorbidities, and cost-effectiveness. Collaboration among healthcare providers is essential for the comprehensive management of DME. Future research should focus on long-term comparative studies, predictors of treatment response, and exploration of novel therapeutic targets to optimize treatment outcomes for patients with DME.