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This retrospective study aimed to compare the efficacy and safety of intravitreal Dexamethasone Implant (DEX) and Brolucizumab Injection in treating Diabetic Macular Edema (DME) with Hyperreflective Intraretinal Dots (HRID). A single-center retrospective study in India included 40 eyes (20 per group) with controlled diabetes and HRID on optical coherence tomography. Patients received either DEX or Brolucizumab, with outcomes assessed at various intervals up to 24 weeks. Primary measures included Best-Corrected Visual Acuity (BCVA), Central Macular Thickness (CMT), and safety parameters. Both treatment groups demonstrated comparable baseline characteristics. Both treatments significantly improved the BCVA at weeks 4, 12, and 24, with the DEX implant showing significantly better results at week 12 than brolucizumab ( =0.04). In treatment-naïve eyes, BCVA improvements were similar across all time points. In recalcitrant DME eyes, DEX showed significant BCVA improvements at all time points, while brolucizumab showed significant improvements only at weeks 4 ( =0.005) and 24 ( =0.04). The CMT also improved with both treatments, with DEX showing superior reduction at weeks 4 ( =0.003), 12 ( =0.003), and 24 ( =0.002) respectively. In treatment-naïve eyes, DEX showed consistently better CMT reductions. In refractory DME eyes, both treatments significantly reduced CMT, with DEX performing better at week 12 ( =0.042). DEX required fewer injections (DEX: 1.5±0.61; brolucizumab: 2.4±0.82; =0.0002) and less supplementary laser treatment (DEX:8/20, 40% eyes; brolucizumab: 16/20, 80%; =0.01) compared to brolucizumab. No adverse events were observed in either group. The study suggests the potential superiority of intravitreal DEX implant over brolucizumab in managing DME with HRID. DEX exhibited sustained positive responses in BCVA and CMT, requiring fewer injections and supplementary interventions. Future research should explore extended follow-up durations, personalized treatment strategies, and refined biomarkers to optimize DME management.