Physiological stresses that can damage proteins are enhanced during pregnancy. For example, hypochlorite, a powerful oxidant released by cells of the innate immune system during inflammatory states including pregnancy, is a potent inducer of protein misfolding. Intuitively, specialised systems which function to maintain protein homeostasis (proteostasis) during pregnancy will exist, but these remain largely uncharacterised. Pregnancy zone protein (PZP) and plasminogen activator inhibitor-2 (PAI-2) are two secreted proteins that are markedly upregulated in humans during pregnancy and in non-pregnancy-associated inflammatory states. Our results show that native PZP and PAI-2 inhibit the aggregation of numerous misfolded proteins including the amyloid beta peptide (Aβ1-42; implicated in the pathology of both Alzheimer’s disease and the pregnancy-specific disorder, pre-eclampsia), and this effect is enhanced by pre-treatment of the putative chaperones with hypochlorite. Accompanying biophysical analyses indicate that hypochlorite treatment induces PZP and PAI-2 to adopt novel conformations with enhanced surface hydrophobicity. Taken together, the available data suggests that PZP and PAI-2 may function as novel members of the extracellular proteostasis network during pregnancy and also in non-pregnancy-associated inflammatory states by operating as hypochlorite-sensitive holdase chaperones. Future work aims to produce a more detailed understanding of the chaperone activities of PZP and PAI-2, which may hold significance for combatting inflammatory protein misfolding disorders, such as Alzheimer’s disease and pre-eclampsia.