The alimentary tract mucosal inflammation has been a topic of concern in oncology; though many modalities of treatment have been proposed for mucosal inflammation, the contributing adverse effects have severely affected the quality of life of patients. This review focuses on the importance of neurogenic peptide, Substance P and its receptor NK-1R in modulating the cascades of events in mucosal inflammation during cytotoxic therapy. There are various preclinical and clinical models showing increased expression of Substance P/NK-1R in ionizing radiation and chemotherapy, but only very few preclinical studies to our knowledge have highlighted or examined its role in mucosal inflammation. Hence, the importance of neuropeptide involved in the inflammatory events in mucosal inflammation in cytotoxic therapy could be a major breakthrough for future research purposes and treatment. The factors contributing to the severity of tissue reactions have been multietiogenic; thus, resultant treatment also has to be directed toward multiple contributing factors. This review also focuses on the significance of care strategy to be adopted in alimentary tract mucositis when multietiogenic factors are taken into consideration.