Although chemotherapy remains the current best practice for the treatment of neoplasia, the severity of its associated side-effects continues to impact detrimentally on the quality of life. Mucositis can affect both the oral cavity and intestine, and represents one of the most common side-effects of chemotherapy. It is characterized by ulceration, inflammation, diarrhoea, and intense abdominal pain. Despite extensive research there remains no definitive therapy for mucositis. This may be due to the multiple factors which contribute to its pathogenesis, including up-regulation of pro-inflammatory cytokines, increased apoptosis of epithelial cells, alteration of the gastrointestinal microbiota, and damage to the epithelium. Although employed increasingly in other gastrointestinal disorders, probiotics are yet to be comprehensively investigated in the treatment or prevention of chemotherapy-induced mucositis. Probiotic-based therapies have been shown to exert beneficial effects, including modulation of the microbiota and inhibition of pro-inflammatory cytokines. This review outlines the current evidence supporting the use of probiotics in intestinal mucositis, and suggests further research directions for the future.