Aim: To evaluate the effect of the prebiotic (PREB) mannan oligosaccharide (MOS) on the progression of the experimental periodontitis (EP) and intestinal morphology in rats. Materials and Methods: Forty rats were randomly allocated into groups (n = 10): C (control), PREB, EP and EP-PREB. Groups PREB and EP-PREB received MOS incorporated into the feed daily. After 30 days, groups EP and EP-PREB received a cotton ligature around their mandibular first molars, kept for 14 days. Morphometrical, histomorphometrical, microcomputed tomography, gene expression analyses and immunohistochemistry were performed. Data were statistically analysed (p < 0.05). Results: Group EP-PREB showed less interproximal bone loss, area without bone in the furcation and bone porosity, and greater bone mineral density than group EP (p < 0.05). It was also observed a significant decrease in IL-10 and IFN-γ gene expression, besides a decrease in TNF-α and IL-1β and an increase in TGF-β immunolabeling score for group EP-PREB. Group EP-PREB also presented villous height and crept depth values similar to group C, while group EP presented reduced values (p < 0.05). Conclusion: It can be concluded that the oral administration of MOS promotes a protective effect against alveolar bone loss caused by EP in rats, modifying histologic and immune-inflammatory parameters, in addition to protecting the intestine.