Effects of ultrasonication, boiling, steaming, microwaving and autoclaving pretreatments on the production of sweet potato protein hydrolysates (SPPH) by single and combined Alcalase (ALC) and Protease (PRO) were investigated, as well as antioxidant activities of SPPH subjected to in vitro gastrointestinal digestion (GID). All pretreatments significantly increased the degree of hydrolysis (DH) and antioxidant activities of SPPH by ALC, PRO and ALC + PRO in the order of autoclaving > steaming, microwaving, boiling > ultrasonication (P < 0.05). GID significantly enhanced antioxidant activities and increased MW <3 kDa peptide fraction contents of all SPPH. Diverse peptides were identified as sporamin A, A precursor and sporamin B before and after GID from LC-QTOF-MS/MS analysis. Peptides with higher antioxidant amino acids of Trp, Tyr, Met, Cys, His and Phe were found after GID. There is a great potential application of SPPH as a novel food ingredient as a natural antioxidant.