Objective To explore the effects of Lactobacillus rhamnosus CQFP202412 on improving the intestinal barrier, liver, brain neurons, and motor function in mice through its antioxidant and anti-inflammatory activities.Methods A mouse model was established by intraperitoneal injection of a mixed antibiotic solution (neomycin 5 mg/mL, vancomycin 25 mg/mL, amphotericin B 0.1 mg/mL, ampicillin 10 mg/mL, metronidazole 5 mg/mL, and lipopolysaccharide 1.5 μg/mL), followed by intervention with L. rhamnosus CQFP202412. After the intervention, weight-loaded swimming time and running exhaustion time were measured, along with liver index and oxidative stress/inflammatory markers in serum and brain tissue. Histopathological changes in the brain were observed by HE staining, and PCR was used to detect the expression of genes related to inflammatory pathways in the brain and key genes of the intestinal barrier.Results Compared with the model group, both live and heat-killed L. rhamnosus CQFP202412 significantly prolonged the weight-loaded swimming time and running exhaustion time in mice (P < 0.05). Body weight changes were not significant, while the liver index significantly decreased (P<0.05). Histological analysis showed that the morphology of cortical neurons was restored. MDA, IL-6, and TNF-α levels in serum and brain were significantly reduced (P < 0.05), while SOD, GSH, and IL-10 levels were significantly increased (P<0.05). Gene expression of the AKT/CREB/BDNF/ERK1 signaling pathway in the brain was significantly upregulated (P < 0.05), and IL-6 gene expression was significantly downregulated (P < 0.05). The expression levels of ZO-1, Occludin-1, and Claudin-1 genes in the cecum were significantly increased (P < 0.05), with Occludin-1 reaching 1.26 and 1.46 times higher than that of normal mice. No significant differences were observed between live and heat-killed L. rhamnosus CQFP202412 in the above results.Conclusion Both live and heat-killed L. rhamnosus CQFP202412 can significantly alleviate antibiotic-induced impairments in motor function, liver and intestinal barrier damage, and oxidative inflammation in the central nervous system of mice (P<0.05), with similar efficacy. These findings suggest that L. rhamnosus CQFP202412 has promising application potential in the development of functional probiotics.