Alzheimer's disease (AD) presents a complex challenge, increasingly linked to the gut microbiota’s role in its development. This study examines changes in the gut microbiome of AD patients, focusing on the reduction of certain bacteroides strains and their metabolite, MEDICA, known for anti-inflammatory effects. However, its direct influence on AD pathology is unclear. We suggest that MEDICA supplementation might improve cognitive function by interacting with the brain-gut axis. To explore this, we assessed the impact of MEDICA on amyloid plaque formation and neuroinflammation. Our results indicate that MEDICA could be beneficial in reducing AD pathologies. Specifically, we observed notable reductions in neuroinflammation in microglia and improved cognitive function in AD mice, as demonstrated in Morris water maze and novel object recognition tests. Additionally, there was a significant decrease in amyloid plaque formation in the group treated with MEDICA compared to the control group. In summary, our findings suggest that MEDICA has the potential to alleviate cognitive impairments and reduce amyloid plaque accumulation, underscoring the gut-brain axis’s importance in AD. These results encourage further investigation into the relationship between gut microbiota and neurodegenerative disorders, presenting a promising direction for AD treatment strategies. This study offers important insights into the complexity of the gut-brain axis and its relevance in effectively understanding and managing AD.