It is noted that Dioscorea quinqueloba is a medicinal herb that is widely used to treat cardiovascular disease and is assessed as useful to treat other various medical conditions. The immunopotentiating effects of the protein extract (DQP-1) from Dioscorea quinqueloba were thus formally investigated in vivo under incident of cold stress. In this case study, the spleen and thymus weight in mice was shown to have decreased after a measured exposure to cold stress, while the adrenal gland weight in the mice was shown to have increased. The systematic oral administration of DQP-1 significantly recovered the weight loss of the spleen and suppressed the adrenal gland hypertrophy during the association with cold stress. Additionally, the DQP-1 also restored the ascorbic acid level in the adrenal gland reduced after cold stress. The cold stress exposure lowered the percentage of CD4+ and CD8+ cells in the mouse thymus as determined by the flow cytometric analysis, as well as the levels of some serum immunological cytokines(interleukin-2, interleukin-12, and interferon-γ) in the studied mice. The resulting identified weakened immunity caused by cold stress was also recovered by a treatment with DQP-1. The DQP-1 significantly suppressed the formation of serum enzymes of alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, which were systematically elevated during the cold stress episode. These results indicate that DQP-1 can improve immunity in mice that are characteristically weakened under stress.