Gut microbiota changes correlate with health status. Literature data on gut microbiota show that all dietary changes can induce the alteration of gut microbiota composition. Mediterranean diet (MD) is associated with a reduction of all-cause mortality and in this review, we analyzed its interactions with human microbiota. In particular, we explored the modulation of the human microbiota, in response to MD adherence, focusing the attention on polyphenols, polyunsaturated fatty acids (PUFA) ω-3 and fiber. Evidences suggest that MD is able to modulate the gut microbiota, increasing its diversity. In fact, a Mediterranean-type dietary pattern is associated with specific gut microbiota characteristics. The available evidence, suggests that gut microbiota of subjects that follow a MD is significantly different from subjects that follow a Western diet model. In fact, the latter show an increased gut permeability, which is responsible for metabolic endotoxemia. For this reason, we can speculate that the gut microbiota of the subjects following a MD is able to prevent the onset of chronic non-communicable degenerative diseases, such as cardiovascular diseases and some types of cancer. However, in order to understand these correlations with dietary patterns, controlled intervention studies on the gut microbiota composition and activity are needed.