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A potentially novel probiotic strain, YY-112, was previously isolated and identified as <i>Lactiplantibacillus pentosus</i> using 16S rDNA sequencing. The whole genome analysis showed that strain YY-112 has the potential to metabolize carbohydrates in the gastrointestinal environment and to regulate immunity. Further, comparative genomics analysis revealed that strain YY-112 was <i>Lactiplantibacillus plantarum</i> (<i>L. plantarum</i>) with more unique genes. The results of in vivo tests showed that <i>L. plantarum</i> YY-112 had no adverse effects and restored the damaged spleen and intestinal barrier of immunocompromised mice. <i>L. plantarum</i> YY-112 recovered the normal levels of lymphocytes, serum cytokines (Interferon-γ, tumor necrosis factor α, and interleukin-6), immunoglobulins (Ig) (IgA, IgM, and IgG) and lipids (albumin, cholesterol, triglyceride). Additionally, <i>L. plantarum</i> YY-112 might indirectly enhance the immune system by improving the intestinal microbiota structure. These results supported the potential of <i>L. plantarum</i> YY-112 as a probiotic to regulate the immune system of hosts.