This study aims to determine the immunomodulatory effects of a polysaccharide fraction from fermented M. citrifolia L. (FMP) in RAW 264.7 macrophages and Balb/c mice. M. citrifolia was fermented for 72 h using Lactobacillus brevis; polysaccharides were extracted using ethanol precipitation. The RAW 264.7 cells exposed to FMP (50, 100, and 200 μg/mL) for 24 h showed increased NO production, proinflammatory cytokine (IL-1β, IL-6, and TNF-α) release, and COX-2 and iNOS protein expression. FMP (100, 200 mg/kg) and deacetylasperulosidic acid (DAA) (20 mg/kg) administered orally to Balb/c mice for 14 days upregulated NO production and NK cytotoxicity in abdominal cavity and spleen, respectively. Th1 and Th2 cytokines production and immune cell numbers increased in spleen, mesenteric lymph nodes (MLN), peritoneal exudate cells (PEC), Peyer’s patches (PP), and peripheral blood mononuclear cells (PBMC). Therefore, FMP containing DAA can be used as materials for health functional foods to enhance immune responses.