Throughout their cancer treatments, around half of all patients will undergo irradiation that is accompanied by several side effects reducing their quality of life and leading to the interruption or extension of their treatment course. Pelvic irradiation leads to the triggering of mucositis and dysbiosis, further impairing the daily life of the patients. In this work, we address the ability of Limnospira indica strain PCC 8005 and Lacticaseibacillus rhamnosus GG ATCC 53103 in alleviating the above-mentioned side effects triggered by the local pelvic irradiation of 12 Gy in a mouse model. We found that the combinatorial administration of these food supplements was able to confer partial tight junction protection while the bacterial translocation towards the mesenteric lymph nodes was found to be identical between the saline sham-irradiated and supplemented irradiated group. Furthermore, the supplemented group did not present a significant shift in microbial composition following pelvic irradiation, indicating that the bacterial formulation was able to mitigate the dysbiosis induced by the latter treatment, as observed in the saline irradiated group. These very promising results will be further completed by investigating the mode of action and/or active molecules mediating the beneficial effects of both L. indica PCC 8005 and L. rhamnosus GG.