<p>Global mango production exceeds 55&#xa0;million tonnes annually, generating large volumes of processing residues that remain poorly valorized despite their high lignocellulosic and biochemical richness. Existing reviews on mango waste utilization are predominantly application-driven and fragmented, offering limited integration of biomass fractionation logic, conversion severity, and downstream functionality thereby constraining rational biorefinery design and scalable translation. This review critically evaluates mango waste streams-peel, seed kernel, seed shell, pulper waste, and leaves as renewable feedstocks within circular bioeconomy and waste-to-wealth frameworks. Adopting a biomass conversion-oriented perspective, it systematically links distinct waste fractions to thermochemical, biochemical, and physicochemical pathways, encompassing the recovery of pectin, polyphenols, starch, lipids, and other bioactives alongside energy and material routes such as bioethanol, biogas, pyrolysis-derived intermediates, biodegradable packaging, cellulose derivatives, and single-cell proteins. Comparative analysis reveals how extraction chemistry, pretreatment intensity, and process severity govern yield-structure-function trade-offs, directly influencing product performance and pathway compatibility within integrated systems. Evidence on therapeutic bioactivities of mango waste–derived compounds is synthesized within a pre-translational context, while explicitly addressing limitations related to extract standardization, bioavailability, and clinical maturity. Key bottlenecks including feedstock heterogeneity, scale-up constraints, regulatory readiness, techno-economic feasibility, and life cycle sustainability are critically examined. This review advances a systems-level framework for cascade mango waste valorization, providing process-informed guidance for the development of robust, scalable, and sustainable mango-based biorefineries.</p>