Mucositis is a common side-effect of cancer chemotherapy and radiotherapy. Features of mucositis include erythema, ulceration, and inflammation of the gastrointestinal tract accompanied by clinical symptoms of abdominal pain and digestive disturbances. New treatment strategies are required. Experimental evidence is accumulating showing therapeutic promise for new nutraceutical agents including probiotic bacteria, probiotic-derived factors, prebiotics, and plant extracts. However, the targeted development of new combinations of these agents (synbiotics) to combat mucositis remains largely unexplored. The current review addresses the potential for these nutraceutical agents to reduce the severity of chemotherapy-damaged mucositis by strategically aligning their underlying mechanism of action with features of mucositis pathogenesis. The potential for certain plant extracts to act as prebiotics, in combination with probiotics or their derived factors, is further investigated. These unique synbiotic formulations could form the basis of a new naturally sourced adjunctive approach to cancer chemotherapy.