The study aimed to investigate the immunomodulatory activity of oligopeptides derivedfrom oat (Avena Nuda L.) (OOPs). Healthy female BALB/c mice were randomly assigned to fivegroups, given deionized water (control) and 0.25, 0.5, 1.0, and 2.0 g/kg body weight (BW) of OOPsdaily by intragastric administration. Seven assays were performed to determine theimmunomodulatory effects of OOPs on immune organ ratios, cellular and humoral immuneresponses, macrophage phagocytosis, and natural killer (NK) cell activity. Spleen T lymphocytesubpopulations (by flow cytometry), serum cytokine and immunoglobulin levels (by multiplexsandwich immunoassays) were determined to evaluate how OOPs affected the immune system.Our results showed that OOPs could significantly improve innate and adaptive immune responsesin mice through the enhancement of cell-mediated and humoral immunity, macrophagephagocytosis capacity, and NK cell activity. We concluded that the immunomodulatory effectsmight be attributed to increased T and Th cell percentages, serum interferon (IFN)-γ, interleukin(IL)-1 α, IL-2, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)- α, and granulocyte-macrophagecolony-stimulating factor (GM-CSF) secretions as well as immunoglobulin (Ig) A, IgG, and IgMproductions. These results indicate that dietary OOPs could be considered as promisingimmunomodulators with dosages ranging from 0.25 to 2.0 g/kg BW.