Background and aim <p>Neuroinflammatory mechanisms have been closely related to the microbiota-gut-brain axis and could lead to degeneration of dopaminergic neurons with subsequent development and progression of Parkinson’s disease (PD). Targeting this pathway for the treatment of PD has sparked a lot of interest. Hence, this study investigates the therapeutic potential of a synbiotic supplement, in conjunction with <span>l</span>-dopa for the management of PD.</p> Methods <p>This randomized controlled trial enrolled 66 Parkinson's disease patients, who were randomly assigned to two groups: a control group (<i>n</i>&#xa0;=&#xa0;33) receiving standard <span>l</span>-dopa/carbidopa (100/25 mg) therapy three times daily for three months, and a synbiotic group (<i>n</i>&#xa0;=&#xa0;33) receiving the same <span>l</span>-dopa/carbidopa regimen with two sachets of the synbiotic supplement daily for three months. The outcome measures included assessment of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and serum levels of tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), brain-derived neurotrophic factor (BDNF), and α-synuclein (α-Syn). Blood samples were collected from all patients for biomarker analysis in serum.</p> Results <p>Three months after intervention, the synbiotic group demonstrated significantly greater improvement in motor and non-motor symptoms compared to the control group evidenced by the change in the scores of each part of the MDS-UPDRS. Concurrently, the synbiotic group exhibited significantly lower serum levels of pro-inflammatory marker TNF-α and oxidative stress marker MDA, and significantly higher levels of the neuroprotective factor BDNF.</p> Conclusion <p>Supplementing with synbiotics exhibits promising neuroprotective and therapeutic effects in the treatment of Parkinson’s disease patients.</p> Clinicaltrials.gov registration number <p>NCT05576818. Retrospectively registered in October 2022.</p>