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The high mortality and morbidity rates of malaria remains to be a global problem, particularly in tropical regions. Cerebral malaria, the leading cause of death, possesses a complex pathogenesis involving host immune and parasite interactions. Lately, according to the gut-brain axis concept, the gut microbiota was identified to protect the host against systemic pathogen infection through the modulation of immune signaling pathways. In this study, we aimed to explore the effect of probiotic supplementation toward neurological outcomes of cerebral malaria in vivo. Twenty-eight male C57BL/6 mice were randomly divided into 5 groups after 2 weeks acclimatization period. All groups except the negative control were given oral probiotic supplementation with either Lactobacillus casei at 109 colony forming unit/100 µL (CFU/100 µL), Bifidobacterium longum at 109 CFU/100 µL, or the combination of each at 5x108 CFU/100 µL for five days before to six days after Plasmodium berghei infection. Neurological manifestations were recorded by using the SmithKline, Harwell, Imperial College, Royal Hospital, Phenotype Assessment (SHIRPA) score. The data was analyzed by using One-way ANOVA and post-hoc LSD. The results showed that there were significant differences of motor behavior (P < 0.01), muscle tone (P < 0.01), reflex and sensory (P < 0.05), and neuropsychiatric state (P < 0.05) between the control group and that receiving combination of L. casei and B. longum. The results suggested that probiotic supplementation showed promising effects in improving the neurological manifestations during cerebral malaria. Further studies are required to explicate the pathways involved in the immunological interplay. In the future, it is propitious that the mortalities by cerebral malaria could be mitigated through the optimal use of probiotics. [ABSTRACT FROM AUTHOR]