<p>Parkinson’s disease (PD) is characterized by dopaminergic neurodegeneration and increasingly associated with gut microbiota alterations. <i>Roseburia intestinalis</i> (<i>R. intestinalis</i>) is consistently reduced in PD; however, its functional contribution remains unknown. We performed two complementary mouse experiments using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced PD model. In the primary intervention experiment, mice received live or heat-killed <i>R. intestinalis</i>, followed by behavioral assessments and multi-layer analyses, including immunofluorescence, western blotting, enzyme-linked immunosorbent assay, quantitative polymerase chain reaction, 16S rRNA sequencing, metabolomics, and transcriptomics. In a separate mechanistic experiment, subdiaphragmatic vagotomy was introduced to interrogate vagus-dependent gut–brain communication, with key behavioral and inflammatory endpoints assessed. Live <i>R. intestinalis</i> improved rotarod, pole, and grip strength performance and preserved tyrosine hydroxylase–positive neurons in the substantia nigra; however, these effects were not observed in the heat-killed group. Live <i>R. intestinalis</i> treatment also reduced glial reactivity, restored brain-derived neurotrophic factor expression, and maintained blood–brain barrier integrity. Systemically, <i>R. intestinalis</i> lowered serum lipopolysaccharide, tumor necrosis factor-α, and interleukin-6 levels; preserved colonic structure; and restored mucin-secreting goblet cell function. MPTP-induced dysbiosis was partially corrected. Metabolomic profiling revealed restoration of several acyl-carnitines and higher acetic acid levels. Transcriptomic analysis showed increased immediate early genes after MPTP, and the elevated c-Fos in the substantia nigra was partially normalized by <i>R. intestinalis</i>. Importantly, vagotomy abolished the central neuroprotective and anti-inflammatory effects but did not affect peripheral cytokine suppression, indicating both vagus-dependent and vagus-independent pathways. <i>R. intestinalis</i> supplementation alleviated motor impairments, reduced neuroinflammation, preserved dopaminergic neurons, and improved intestinal and metabolic alterations in mice with an MPTP-induced PD model. Its protective actions may involve both central and peripheral mechanisms, potentially including gut–brain communication pathways. <i>R. intestinalis</i> may be a promising candidate for microbiota-based strategies against PD.</p> Graphical Abstract <p></p>