Angiogenesis, the process of forming new blood vessels from existing ones, is essential for normal physiology but becomes dysregulated in diseases like cancer, neovascular eye conditions, and chronic inflammation. This chapter explores the significant potential of microRNAs (miRNAs) as antiangiogenic agents and their promise in combination therapies to enhance treatment efficacy beyond current monotherapies. It begins by outlining critical pro-angiogenic signaling pathways such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), which drive endothelial cell proliferation and vessel remodeling. Key criteria for selecting effective, particular antiangiogenic miRNAs are discussed, alongside comprehensive evidence from in vitro and in vivo studies demonstrating their ability to inhibit endothelial proliferation, migration, and tube formation in tumor and retinal models. Detailed coverage of diverse miRNA delivery systems, including lipid and polymer nanoparticles, viral vectors, exosome-based carriers, and innovative stimuli-responsive platforms, is provided, assessing their efficacy, safety, and translational potential along with crucial preclinical and clinical findings.