Lactococcus lactis subsp. lactis KCCM13334P (KMGR) was isolated from Makgeolli, a traditional Korean rice wine. The study analyzed the genomic characteristics and performed functional annotation of the complete genome sequence. Results showed that IFN-γ-primed RAW 264.7 cells, treatment with KMGR (6.25, 12.50, or 25.00 μg/mL) significantly enhanced immune response mediator and cytokines production. KMGR significantly activated NF-κB and AP-1 signaling pathways. KMGR improved macrophage activity by stimulating TAK1 and TRAF6 via TLR2 signaling. In CTX-induced immunosuppressed mice, KMGR administration recovered body weight and spleen and mesenteric lymph node indices. KMGR restored CTX-suppressed natural killer cell activity and populations of immune cells. Additionally, KMGR repaired the CTX-induced histological structure of the colon and the expression of tight junction proteins, mucin-2, and TLR2. KMGR treatment maintained a gut microbiota composition similar to the control groups. Taken together, our data suggest that KMGR shows potential as a functional postbiotic with immune-enhancing activity.