Summary The objectives of this study were to determine the optimal extraction conditions of polyphenols from Syzygium cumini seeds by response surface methodology and investigate their antioxidant activity and inhibition on α‐amylase and pancreatic lipase. As results, the optimal extraction conditions in the ultrasonic extraction process which maximised total polyphenols content, minimised the IC50 values of α‐amylase and pancreatic lipase were determined as follows: extraction time 60 min, ethanol concentration 63% and solvent/solid ratio 44 mL g−1. The main phenolic compounds in partially purified fraction of Syzygium cumini seeds were catechin, epicatechin, kaempferol, gallic, 5‐caffeoylquinic, caffeic and ferulic acids. In addition, the partially purified fraction inhibited 87.66 ± 5.55 and 86.61 ± 3.15% of α‐amylase and pancreatic lipase, respectively. The results suggested that Syzygium cumini seeds could be explored as a natural antioxidant and could be used as a source of highly antidiabetic and anti‐obesity bioactive compounds. BBD could be used as an initial efficient design for the extraction of desired bioactive compounds with high antioxidant activity and inhibition on A‐amylase and PL.