SCOPE: Targeting gut microbiota dysbiosis by prebiotics is effective, though side-effects such as abdominal bloating and flatulence may arise following high prebiotic consumption over weeks. Our aim was therefore to optimize the current protocol for prebiotic use. METHODS AND RESULTS: To examine the prebiotic properties of plant extracts, we conducted two independent studies in ob/ob mice, over two weeks. In the first study, we evaluated Porphyra umbilicalis and Melissa officinalis L. extracts; in the second study, we assessed a high- vs. low-dose of an Emblica officinalis Gaertn extract. These plant extracts affected gut microbiota, caecum metabolome and induced a significant lower plasma triacylglycerols (TG) following the treatment with P. umbilicalis and significant higher plasma free fatty acids (FFA) following treatment with the low-dose of E. officinalis Gaertn. Glucose- and insulin-tolerance were not affected but white adipose tissue and liver gene expression were modified. In the first study, IL-6 hepatic gene expression was significantly (adjusted P = 0.0015) and positively (r = 0.80) correlated with the bacterial order Clostridiales in all mice. CONCLUSION: Our data show that a 2-week treatment with plant extracts affects the dysbiotic gut microbiota and changes both caecum metabolome and markers of lipid metabolism in ob/ob mice.