<b>Background:</b> The immunomodulatory effects of mesenchymal stem cells (MSCs) and their exosomes have been receiving increasing attention. This study investigated the immunoregulatory effects of human amniotic mesenchymal stem cells (hAMSCs) and their exosomes on phytohemagglutinin (PHA)-induced peripheral blood mononuclear cells (PBMCs). <b>Methods:</b> The hAMSCs used in the experiment were identified by light microscopy and flow cytometry, and the differentiation ability of the cells was determined by Oil Red O and Alizarin Red staining. The expressions of transforming growth factor (TGF)-β, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2 (COX-2), hepatocyte growth factor (HGF), and interleukin (IL)-6 were detected by quantitative real-time polymerase chain reaction and western blotting. PBMCs, hAMSCs, and their exosomes were collected for <i>in vitro</i> group culture. Then the immunoregulatory ability of hAMSCs and their exosomes were analyzed by flow cytometry and Enzyme-linked immunosorbent assay. <b>Results:</b> The hAMSCs and exosomes were successfully extracted from the human amniotic membrane. TGF-β, IDO, COX-2, HGF, and IL-6 were significantly expressed in hAMSCs. <i>In vitro</i> co-culture showed that hAMSCs promoted the proliferation of Th2 cells in PHA-induced PBMCs, while hAMSCs and exosomes inhibited the secretion of TNF-α in PHA-induced PBMCs, and promoted the secretion of IL-4 and IL-10, and hAMSCs had more significant effects than exosomes. <b>Conclusions:</b> hAMSCs or exosomes could exert immunoregulatory effects on PHA-induced PBMCs by affecting Th2 cell proliferation and cytokine secretion.