In order to increase the bioavailability of mountain ginseng (MG), gold nanoparticles (MG-AuNPs) were biologically synthesized from MG extract, and an oil-in-water (O/W) nanoemulsion (SMG-AuNEs) was prepared from MG-AuNPs and a phytochemical silydianin. The physical stability of SMG-AuNEs were monitored and optimized in terms of particle size, pH value, zeta potential, and polydispersity index. The chemicostructural properties of the prepared MG-AuNPs and SMG-AuNEs were characterized using various spectrometric and microscopic analyses, such as EDX spectroscopy, FT-IR spectroscopy, and TEM. The effect of both nanomaterial samples on the anti-inflammatory activity and their underlying mechanism was compared in LPS-stimulated RAW 264.7 cells. SMG-AuNEs did not show toxic effects against RAW 264.7 macrophages, HaCaT keratinocytes, and normal dermal fibroblasts. SMG-AuNEs exhibited significantly higher inhibition of pro-inflammatory genes and proteins, including IL-1β, IL-6, and TNF-α, compared with those of MG-AuNPs and silydianin. Western blotting analysis revealed that the MAPK and NF-κB signalings were highly inhibited by SMG-AuNEs treatment. Hence, this study shows that nano-emulsification of gold nanoparticles prepared from MG is a useful method for augmenting the anti-inflammatory potential of MG. This study may serve as a foundation for using MG as a functional ingredient in anti-inflammatory agents. Our results may implicate the use of nanoemulsions to develop new anti-inflammatory products using MG.