Introduction and Objectives Mucositis, a common side effect of cancer chemotherapy, is a clinically important gastrointestinal inflammatory disease. It consists in a painful inflammation and ulceration of the digestive mucosa, which may compromise proper nutrition of the patient, as well as termination of the treatment. It thus increases mortality and morbidity and contributes to rising health care costs. Its treatment is mainly supportive and often fails to relieve symptoms. Probiotic bacteria may maintain homeostasis and reduce side effects of chemotherapy [1]. A major limit to probiotic bacteria anti-inflammatory effect is their susceptibility to digestive stresses and several studies indicate the key protective role of food matrices in increasing probiotics’ effect via the protection of bacteria against digestive constraints. In this study, we investigated the role of fermented milk, using the immunomodulatory Lactobacillus casei BL23 [2] or Propionibacterium freudenreichii CB129 [3, 4] as a probiotic starter, and of its fortification via addition of whey proteins. Materials and methods We evaluated the role of whey protein isolate (WPI), when added to skim milk fermented by L. casei BL23 or by P. freudenreichii 138, as a protective matrix against in vitro stress challenges. In addition, we investigated in vivo the therapeutic effect of these fermented beverages in a murine model of mucositis induced by 5-Fluorouracil (5-FU). The monitored outcomes included weight loss, ileum histopathological score, villus height, crypt depth and number of mucus-producing goblet cells. Results This study demonstrated that milk supplementation with 30% (w/v) of WPI increases the survival rate of both strains when challenged with acid or bile salts, compared to fermented skim milk without the addition of WPI. Moreover, treatment with the probiotic beverages prevented weight loss and intestinal damages in mice receiving 5-FU. All symptoms of mucositis were drastically reduced by the consumption of developed probiotic fermented milks [5]. Conclusion This study evidenced the protective effect of selected strains of both lactic and propionic acid bacteria, in the context of induced mucositis. It confirmed that selected strains might be used both as starter and probiotic. It opens new avenues for the development of fermented functional foods for target populations.