Abstract: To investigate the protective effect of Pediococcus pentosaceus CQFP202437 against antibiotic-induced locomotor disorders in mice, and to explore the effect and mechanism of probiotics, a mouse model of dyskinesia was constructed by intraperitoneal injection of sterile mixed antibiotic solution. After the modeling period, changes in exercise parameters such as running and swimming were analyzed in each group of mice, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), interleukin (IL-6, IL-10), and tumor necrosis factor (TNF-α) were measured in the serum and cerebrum of mice. The mRNA expression of cecum intestinal barrier genes Occludin-1, ZO-1 and Claudin-1, and the mRNA expression of CREB, ERK1/2 and BDNF genes in mouse brain were determined. Results indicated that Pediococcus pentosaceus CQFP202437 significantly increased both swimming and running duration in mice compared to the model group (P<0.01). Additionally, this treatment significantly (P<0.05) reduced the levels of inflammatory factors IL-6 and TNF-α in the mouse brain, increased the expression of SOD in the mouse brain, and reduced the accumulation of MDA in the mouse brain and serum. Furthermore, Pediococcus pentosaceus CQFP202437 improved the expression of BDNF, ERK1/2, CREB, and genes associated with the BDNF metabolic pathway in the cerebrum. It also upregulated the expression of the Occludin-1 gene in the cecum, which was crucial for maintaining intestinal barrier integrity and ensuring normal physiological function. These results suggested that a modulating effect on antibiotic-induced locomotor dysfunction in mice was exerted by Pediococcus pentosaceus CQFP202437, providing a theoretical foundation for the development of probiotic formulations aimed at enhancing locomotor function.