Gut brain axis can affect the incidence of Alzheimer's disease (AD). Probiotics restore the homeostasis of gut dysbiosis and prevent AD. Here, we evaluated the impact of Saccharomyces boulardii on rats with lipopolysaccharide (LPS)-induced amyloidogenesis. Rats were classified into four groups: (1) Control (saline), (2) LPS 250 µg/kg (saline + LPS), (3) S. boulardii (10 CFU/mL/rat), and (4) S. boulardii (10 CFU/mL/rat) + LPS (250 μg/kg). The passive behavioral test, Western blotting, and immunohistochemistry were done using the animal hippocampi. Step-through latency (STL) indicated that the LPS-treated group had decreased memory retrieval compared to the control group. The LPS group had increased hippocampal levels of amyloid-β peptide, amyloid-β precursor protein (APP), and β-secretase (BACE). Administration of the S. boulardii before LPS prolonged STL which has been shortened in the LPS group (P < 0.05). In the LPS + S group, S. boulardii reduced the levels of APP significantly compared to the LPS group (P < 0.01). S. boulardii mitigated Aβ buildup and memory dysfunction caused by LPS through modulating the APP, BACE1, and Aβ pathways. Future studies are required to explain the neuroprotective effects of S. boulardii, since it could be a novel therapy or prevention strategy for AD.