Frailty, which is a syndrome that encompasses losses in physical, psychological and social domains, is responsible for enhanced vulnerability to endogenous and/or exogenous stressors. Frailty is a public health problem for an ageing society; however, it is poorly understood and often under-recognised in clinical settings. In particular, the impact of frailty on either intestinal functions, i.e. immune response, permeability, and absorption, or gut microbiota composition is as yet mostly unexplored. A better comprehension of the intestinal dysfunction occurring in the elderly would help in clarifying the mechanisms predisposing frail patients to a higher risk of infectious or inflammatory events. Moreover, recent evidence suggests that senescence-induced perturbations of the gut–brain axis are involved in the neuroinflammation process, thus raising the hypothesis that preserving gut permeability and preventing frailty-related changes in the microbiota composition might reduce the susceptibility to develop neurodegenerative disorders. In this review, we highlight the current insights concerning the relationship between frailty, intestinal functions, microbiota, and gut–brain axis.