The adult gut microbiota contains trillions of microorganisms of thousands of different species. Only one third of gut microbiota are common to most people; the rest are specific and contribute to enhancing genetic variation. Gut microorganisms significantly affect host nutrition, metabolic function, immune system, and redox levels, and may be modulated by several environmental conditions, including physical activity and exercise. Microbiota also act like an endocrine organ and is sensitive to the homeostatic and physiological changes associated with training; in turn, exercise has been demonstrated to increase microbiota diversity, consequently improving the metabolic profile and immunological responses. On the other side, adaptation to exercise might be influenced by the individual gut microbiota that regulates the energetic balance and participates to the control of inflammatory, redox, and hydration status. Intense endurance exercise causes physiological and biochemical demands, and requires adequate measures to counteract oxidative stress, intestinal permeability, electrolyte imbalance, glycogen depletion, frequent upper respiratory tract infections, systemic inflammation and immune responses. Microbiota could be an important tool to improve overall general health, performance, and energy availability while controlling inflammation and redox levels in endurance athletes. The relationship among gut microbiota, general health, training adaptation and performance, along with a focus on sport supplements which are known to exert some influence on the microbiota, will be discussed.