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Plant and fruit extracts exhibit fewer side effects than pharmaceuticals and can display therapeutic qualities. Consequently, they have attracted increased attention among health-conscious individuals, and many studies related to their health-promoting effects are being actively conducted. Vitis coignetiae is well-known for its antioxidant, anti-inflammatory, and anticancer properties. However, the immune-enhancing effects of Vitis coignetiae have not yet been studied. In this study, Vitis coignetiae extract (VCE) increased immune-related activity in Wistar rat splenocytes and cyclophosphamide (Cy)-induced immunosuppressed rats. In splenocytes, VCE was nontoxic up to 300 μg/mL and increased cell viability in the presence of Cy. VCE also recovered Cy-induced decreases in cytokine (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-2 (IL-2), and IL-12) levels and natural killer (NK) cell activity in splenocytes. In Cy-induced immunosuppressed rats, VCE protected against Cy-induced spleen tissue damage and decreases in body and spleen weight, cytokine (TNF-α, IFN-γ, IL-2, and IL-12) levels, and NK cell activity. We also observed recovery of immunoglobulin G (IgG) and IgM levels following VCE treatment. In conclusion, the ability of VCE to restore immune activity from an immunosuppressive state to normal levels suggests its immune-enhancing efficacy. Therefore, VCE may have the potential for application in the development of immune-enhancing functional foods and medicines. [ABSTRACT FROM AUTHOR]