An important role of the gut microbiota has been identified in the complex network of metabolic diseases, which includes obesity and insulin resistance. The composition of various microbes within the gut is dictated by the dietary habits adopted over the years and this then affects the dogma of energy metabolism and sustains obesity. This chapter focuses on current evidence and investigates the advanced mechanisms of the contribution of human intestinal microflora to the metabolic disorders mentioned above. Furthermore, this chapter speculates the effective treatments and future experiments, which could facilitate cancelling the insulin resistance and preventing the consequences related to obesity. Such a comprehensive view may reveal new diagnostic markers of obesity and diabetes mellitus and allow timely diagnosis and treatment.