The tetrapeptides Li504 and Li520, differing in the modification of the 4-trans-hydroxylation of proline, are novel conopeptides derived from the venom duct transcriptome of the marine cone snail Conus lividus. These predicted mature peptides are homologous to the active site motif of oxidoreductases that catalyze the oxidation, reduction, and rearrangement of disulfide bonds in peptides and proteins. The estimated reduction potential of the disulfide of Li504 and Li520 is within the range of disulfide reduction potentials of oxidoreductases, indicating that they may catalyze the oxidative folding of conotoxins. Conformational features of Li504 and Li520 include the trans configuration of the Cys1-Pro2/Hyp2 peptide bond with a type 1 turn that is similar to the active site motif of glutaredoxin that regulates the oxidation of cysteine thiols to disulfides. Li504- and Li520-assisted oxidative folding of α-conotoxin ImI confirms that Li520 improves the yield of the natively folded peptide by concomitantly decreasing the yield of the non-native disulfide isomer and thus acts as a miniature disulfide isomerase. The geometry of the Cys1-Hyp2 peptide bond of Li520 shifts between the trans and cis configurations in the disulfide form and thiol/thiolate form, which regulates the deprotonation of the N-terminal cysteine residue. Hydrogen bonding of the hydroxyl group of 4-trans-hydroxyproline with the interpeptide chain unit in the mixed disulfide form may play a vital role in shifting the geometry of the Cys1-Hyp2 peptide bond from cis to trans configuration. The Li520 conopeptide together with similar peptides derived from other species may constitute a new family of "redox-active" conopeptides that are integral components of the oxidative folding machinery of conotoxins.