Porcine mesenchymal stem cells (MSCs) have been reported as effective methods for overcoming immune rejection of allografts. Specifically, bone marrow-derived mesenchymal stem cells (BM-MSCs) have demonstrated significant immunomodulatory capabilities. Although obtaining BM-MSCs is challenging, peripheral blood-derived mesenchymal stem cells (PB-MSCs) can be easily harvested at any time through a significantly less invasive method. However, the immunomodulatory effects of PB-MSCs are poorly understood. In this study, the characterization of PB-MSCs isolated from peripheral blood mononuclear cells (PBMCs) was confirmed by MSC surface markers CD44, CD73, CD90, and CD105, and they were negative for CD11b and CD45. The results showed that PB-MSCs demonstrated similar potential for cell proliferation and differentiation into various cell types when compared to BM-MSCs. To assess the immunomodulatory effects of BM-MSCs and PB-MSCs, we examined inflammation-related cytokine expression in human monocyte (THP-1) cells treated with phorbol-12-myristate-13-acetate (PMA) and lipopolysaccharide (LPS), and then indirectly co-cultured with MSCs. As a result, M1 macrophage surface markers CD86 and CCR7 were decreased, and the M2 surface marker CD163 was increased, while pro-inflammatory markers TNF-α and IL-6 were decreased and the anti-inflammatory marker IL-10 was increased. Furthermore, xenogenic cytotoxicity assessment results revealed that when porcine cells were directly co-cultured with PMA and LPS-differentiated THP-1 cells educated with MSCs, PB-MSCs demonstrated a greater reduction in xenogenic cytotoxicity compared to BM-MSCs, suggesting the need for further research. Therefore, the more effective immunomodulatory function of PB-MSCs compared to BM-MSCs has been confirmed. In addition, future research will elucidate the molecular mechanisms underlying the immunomodulatory functions of PB-MSCs and evaluate their potential clinical applications in xenotransplantation and cell-based therapies.