The prevalence of overweight and obesity has reached epidemic proportions globally over the past few decades. The search for new management approaches continues and among them, targeting the gut microbiota can be envisioned. To date, numerous data showed the involvement of the gut microbes in the regulation and control of host metabolism. There are also increasing evidences highlighting the interactions between environmental factors, intrinsic factors, gut microbiota, and metabolic diseases. Diet emerges as the most relevant factor influencing the gut microbiome. Eating habits, as well as short-term consumption of specific diets, alter the gut microbiota composition. Moreover, nutritional disorders are associated with changes of the gut microbiota composition and/or function, as shown in obesity or type 2 diabetic patients versus healthy lean subjects. Targeting the gut microbiota for improving metabolic health appears as a new approach to manage obesity and cardio-metabolic risk. In this review, we have detailed the results of human interventions targeting the gut microbiome by prebiotic supplementation, prebiotics being defined as "substrates that are selectively utilized by the host microorganisms conferring a health benefit." If the potential benefit of this approach is obvious in preclinical models, the efficacy of prebiotics in humans is less reproducible. The inter-individual variability of response to dietary intervention can be dependent on the gut microbiota and we summarized the basal gut microbiota characteristics driving the metabolic response to dieting, prebiotic and dietary fiber intervention in the context of obesity and related metabolic diseases.