Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by movement disorders. The main characteristic of PD is the loss or degeneration of dopaminergic neurons in the substantia nigra. The gut microbiota is now recognized as a potential participant in the pathogenesis of PD. This study aims to investigate the effects of Lactobacillus sakei (Ls) on the gut-brain axis and explore the underlying molecular mechanism using a PD model. Probiotics were orally administered for four weeks after MPTP injection. The study observed that Ls significantly improved movement, including walking and tremors, reduced α-synuclein accumulation in the brain, and positively impacted the microbial composition of feces in PD models. The study found that the intervention resulted in a reduction of IL-6 and TNF-α at both mRNA and protein levels, as well as a decrease in TLR4 expression and NF-kB nuclear translocation in the brain. Additionally, the intervention attenuated disruption of the intestinal barrier and blood-brain barrier. The study found a correlation between the gut microbiome and the brain, particularly in relation to probiotic interventions. The mechanism behind this correlation is linked to the inhibition of both the TLR4 and NF-kB signaling pathways, as well as inflammatory responses. Therefore, targeting the gut-brain axis may be a promising approach for developing preventative measures and therapeutic options for PD.