The stem and root bark of Ulmus macrocarpa Hance has been used as traditional pharmacological agent against inflammation related disorders. The objective of this study was to explore the impact of Ulmus macrocarpa Hance extract (UME) on human gut microbiota. A randomized placebo-controlled clinical study was conducted in healthy adults. The study subjects were given 500 mg/day of UME or placebo orally for 4 weeks. Eighty fecal samples were collected at baseline and 4 weeks of UME or placebo intervention. The gut microbiota variation was evaluated by 16S rRNA profiling. The microbial response was highly personalized, and no statistically significant differences was observed in both species richness and abundance. The number of bacterial species identified in study subjects ranged from 86 to 182 species. The analysis for taxonomical changes revealed an increase in Eubacterium ventriosum, Blautia faecis, Ruminococcus gnavus in the UME group. Functional enrichment of bacterial genes showed an increase in primary and secondary bile acid biosynthesis in UME group. Having known from previous studies Eubacterium regulated bile acid homeostasis in protecting gut microbial architecture and immunity, we suggest that UME supplementation might enhance host immunity by modulating gut microbiota. This is the first stage study and forthcoming clinical studies with larger participants are needed to confirm these findings.