Food by-products have been used as source of bioactive compounds with health benefits. Supercritical carbon dioxide (SC-CO2) extraction has been a valuable technology to obtain a diversity of bioactive compounds with the use of safer solvents. This research focused on the comparison of the antioxidant, anti-inflammatory and antihyperglycemic activities of SC-CO2 and conventional extracts obtained from black bean by-products. A Box-Behnken design was used to evaluate the effect of temperature, pressure, and co-solvent on the soyasaponins recovery. Total phenolic compounds (TPC) were quantified using Folin-Ciocalteu. Cellular antioxidant activity (CAA) and anti-inflammatory response via nitric oxide (NO) assay were evaluated in vitro. The antihyperglycemic activity was evaluated using digestive enzymes. The highest soyasaponin extraction yield was obtained at 70 °C, 10 MPa and 10% co-solvent. SC-CO2 extracts exhibited up to 74.7% of CAA, an inhibition of 93.0% NO, 25.1% α-amylase, 78.7% α-glucosidase and 82.33 ± 5.80 of TPC. SC-CO2 extraction resulted in a feasible technology to obtain high-value compounds from industrial by-products to treat hyperglycemic, oxidative stress and inflammation. Display omitted •SC-CO2 mixed with co-solvent is a feasible technique to obtain rich soyasaponins extracts from black bean by-products.•Recovery of Ba (V) and αg soyasaponins from black bean by-product extracts is favored at 70°C, 10 MPa and 10% co-solvent.•Extraction at 55 °C, 10 MPa and 5% co-solvent showed the highest extraction selectivity of Ba (V) and αg soyasaponins.•SC-CO2 with co-solvent is a feasible technique to obtain extracts with a higher content of TPC from black bean by-products.•The antioxidant, anti-inflammatory and antihyperglycemic activities were correlated with soyasaponin Ba (V), αg and TPC.