Hydrolysis parameters affecting the release of dipeptidyl peptidase IV (DPP-IV) inhibitory and antioxidant peptides from milk proteins have not been extensively studied. Therefore, a multifactorial (i.e. pH, temperature and hydrolysis time) composite design was used to optimise the release of bioactive peptides (BAPs) with DPP-IV inhibitory and antioxidant [oxygen radical absorbance capacity (ORAC)] properties from sodium caseinate. Fifteen sodium caseinate hydrolysates (H1-H15) were generated with Protamex Generation of milk protein hydrolysates through multifactorial design approaches may aid in the optimal enzymatic release of BAPs with serum glucose lowering and antioxidant properties. © 2016 Society of Chemical Industry.