<p>Agricultural waste valorization lacks standardized quantitative frameworks for assessing commercial viability of bioactive compounds, particularly in developing economies where resource optimization is critical for sustainable development. This study developed and validated a novel Bioactive Compound Economic Index (BCEI) using Nigerian sweet orange (<i>Citrus sinensis Osberk</i>) peel waste as a model system. Volatile compounds were identified via GC–MS analysis, while antioxidant potential was comprehensively evaluated through six complementary assays (DPPH, FRAP, NOSC, HRS, LPS, and HPS). The BCEI integrated market-based valuation of volatile compounds, therapeutic equivalence units (TEU), and synergistic bioactivity contributions to provide holistic economic assessment. GC–MS analysis identified 17 major volatile compounds, with 2-methoxy-4-vinylphenol (25.44%) and decanal (16.22%) as predominant constituents. Antioxidant assays yielded IC₅₀ values of 67.9–132.4&#xa0;μg/mL, with TEU values ranging from 47.6% to 52.7% relative to ascorbic acid (weighted average TEU: 50.8 ± 2.1%). The BCEI framework generated a total economic value of $333.22/kg extract, comprising volatile compound value ($221.18/kg), antioxidant bioactivity value ($68.58/kg), and synergy bonus ($43.46/kg). Economic projections indicate potential for ₦65–85 billion annual revenue generation and creation of up to 3,750 jobs in Nigeria. The BCEI framework provides a validated, replicable methodology for quantitative assessment of agricultural waste bioactive compounds. The demonstrated commercial viability of orange peel waste (BCEI: $333.22/kg) positions it favorably among agricultural waste sources and supports investment decisions in sustainable bioeconomy development. This framework addresses critical translation gaps between laboratory research and industrial applications, offering standardized tools for evidence-based policy development in agricultural waste valorization.</p> Graphical Abstract <p></p>