In order to figure out the key acylated anthocyanin compounds accounting for the bioprotective activity of purple sweet potato (Ipomoea batatas L.), ODS packing column, semi-preparative HPLC method, activity evaluation assays, and ultra-high-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) assays were employed. Additionally, our study revealed that the structures of two acylated monomeric anthocyanins, cyanidin 3-caffeoyl-feruloyl sophoroside-5-glucoside and peonidin 3-dicaffeoyl sophoroside-5-glucoside were found to have the strongest bioprotective activity, which was identified to be closely related with the ortho-dihydroxybenzene structure, suggesting the more the special structures of catechol moieties, such as caffeoyl and cyanidin, the stronger the bioprotective activity will be. Besides, the aglycon of cyanidin had higher antioxidant capacity than the peonidin, and the acylated residues strengthened the capacity which followed the order of caffeoyl>feruloyl>p-hydroxybenzoyl. These results will lay the groundwork for further researching the structure-activity relationships of acylated monomeric anthocyanins from purple sweet potato.