To enhance the physiological activity of the Rhynchosia volubilis (RV), R. volubilis (RVHE-A) and R. volubilis-added herbal powder (RVHE-B) were fermented with a solid state culture of Hericium erinaceum mycelia (HE). The total isoflavone contents of the non-fermented RV-A (489.9 μg/g) and RV-B (571.1 μg/g) were remarkably increased in fermented RVHE-A (1,836.4 μg/g) and RVHE-B (1,276.7 μg/g). In particular, aglycone isoflavones such as daidzein and genistein were significantly higher in the RVHE-A than any other sample. When hot-water (HW) and EtOH extracts (E) were fractionated from the RV and RVHE, both extracts from the RVHE-A were higher than those from the RV-A in total polyphenol and flavonoid contents. However, the RVHE-B-HW showed a lower polyphenol and flavonoid content level than did RV-B-HW. RVHE-A-HW and -E also had more potent ABTS radical scavenging activity than any extract from the non-fermented RV and other ferments (RVHE-B). In the meanwhile, RVHE-A-HW potently stimulated the production of macrophage activation-related cytokines such as TNF-α, IL-6 and IL-12 (841.7±71.3 pg/mL, 3.9±0.1 ng/mL, 179.3±30.2 pg/mL) from peritoneal macrophage more than RV-A-HW (92.5±1.5 pg/mL, 0.1±0.0 ng/mL, 37.4±5.4 pg/mL) as well as RVHE-B-HW (557.0±21.3 pg/mL, 1.8±0.0 ng/mL, 90.0±10.0 pg/mL). However, all the EtOH extracts did not show significant activity. In addition, the RVHE-A-HW showed a significantly higher intestinal immune system modulating activity through Peyer’s patch and GM-CSF production than did any other extract from RV and RVHE-B. In conclusion, these results suggest that the fermented R. volubilis with H. erinaceum mycelia possesses a possible use as an industrial application as functional food or material.