Parkinson’s disease (PD) is a complex neurodegenerative disorder with debilitating non-motor symptoms, including gastrointestinal dysfunction, cardiovascular abnormalities, mood and anxiety disorders, cognitive decline, sleep disturbances, respiratory dysfunction, and pain. Despite their significant impact on quality of life, these symptoms are often inadequately addressed. Propolis is a natural bee-derived product, rich in bioactive compounds with anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective properties, which holds potential in PD due to its multitarget and multipathway actions, addressing various underlying mechanisms of non-motor symptom diseases. Preclinical and clinical studies suggest that propolis may influence key pathological mechanisms in PD’s non-motor symptoms. Evidence points to its potential benefits in improving cognition, mood disorders, gastrointestinal health, and alleviating cardiovascular and sleep-related issues. Although research on propolis in non-motor symptoms of PD remains scarce, findings from related conditions suggest its ability to influence mechanisms associated with these symptoms. This review underscores the underexplored therapeutic potential of propolis in non-motor symptoms of PD, drawing on existing evidence and advocating for further research to fully assess its role in addressing these symptoms and improving patient outcomes.

Parkinson’s disease (PD) is characterized by progressive nigrostriatal degeneration and striatal dysfunction, yet its metabolic remodeling remains incompletely defined. Here, untargeted GC–MS metabolomics was used to investigate the effects of standardized Brazilian green propolis on the striatal metabolic profile in the 6-hydroxydopamine (6-OHDA) rat model. Discriminant metabolites, including suberic acid, gluconic acid, heptadecane, and tartaric acid, distinguished experimental groups, capturing key features of the metabolic response to dopaminergic injury and treatment. Suberic acid emerged as a prominently modulated metabolite, potentially linked to alterations in lipid catabolism associated with mitochondrial–peroxisomal pathways. Propolis treatment attenuated the elevation of suberic acid, accompanied by a reduction in gluconic acid levels, suggesting a metabolic profile linked to pathways involved in redox balance and glucose handling. Given previous reports identifying heptadecane as a hydrocarbon constituent of volatile propolis fractions, complementary GC-Q-TOF analyses demonstrated that heptadecane was absent from the administered extract, despite its consistent association with propolis-treated groups. Metabolic changes were accompanied by attenuation of nigrostriatal dopaminergic neurodegeneration and improved motor performance. Together, these findings delineate a striatal metabolic signature associated with Brazilian green propolis and identify suberic acid as a key metabolite linked to neuroprotection in experimental Parkinsonism.