Abstract: This study evaluated the immunomodulatory potential of 20 strains of probiotics screened from traditional plant-derived fermented foods. The purpose of this paper was to develop a probiotic with immunomodulatory function and explore its immune enhancement effect. BALB/c mice were injected with cyclophosphamide to establish an immunosuppressed mouse model, and probiotics were given orally for 21 days. The improvement of immunosuppressed mice was evaluated by measuring the immune indexes of mice. The results showed that among 20 strains of probiotics, Lactiplantibacillus plantarum K8, Lactiplantibacillus plantarum H8, Bacillus subtilis D1 and other strains improved the body weight, thymus index, white blood cells and platelets in immunosuppressed mice to varying degrees. The strongest immunomodulatory impact was exhibited by K8. K8 increased the number of white blood cells, red blood cells, hemoglobin, and platelets in the blood, enhanced bone marrow suppression, and improved thymus and spleen index abnormalities in immunocompromised mice. In addition, K8 reduced the oxidative stress reaction of the liver and increased the levels of immunoglobulin and inflammatory cytokines in the serum of mice. Intestinal microflora results showed that K8 improved the relative abundance of Muribaculaceae and Lactobacillus in mice, corrected the abundance and structure of intestinal microflora, and restored the intestinal microecological imbalance in immunosuppressed mice. In conclusion, Lactiplantibacillus plantarum K8 may be a probiotic that can boost the immune systems of impaired mice. The theoretical foundation for developing probiotic products with immunomodulatory action and further exploiting the probiotic resources found in traditional fermented food will be laid by this study.