<p>The glymphatic system, a network of perivascular channels in the brain, clears toxins and metabolic products such as amyloid-β (Aβ), supporting cognitive function and preventing neurodegenerative diseases. The gut microbiome also affects brain health and cognitive functions by producing anti-inflammatory metabolites and neurotransmitters. In this narrative review study, recently published articles from reputable scientific databases were collected and analyzed. Characteristics related to the gut microbiome, its metabolites, and their impact on the glymphatic system and ultimately cognitive function were examined. These findings indicate that microbial metabolites such as short-chain fatty acids (SCFAs) and neurotransmitters such as serotonin and melatonin reduce brain inflammation and improve sleep quality and synaptic plasticity, which are essential for memory stabilization. Disruption of the gut microbiome (dysbiosis) leads to increased inflammation and dysfunction of the glymphatic system, resulting in the accumulation of toxic proteins and decreased cognitive function. Proper polarization of aquaporin-4 (AQP4), a water channel protein critical for fluid homeostasis in the brain, in astrocytes is essential for the effective functioning of this system, and its disruption is associated with diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Understanding the interaction between the gut microbiome and the glymphatic system presents a new pathway for regulating memory and cognitive health, which could be an important target for the prevention and treatment of neurodegenerative diseases. Enhancing the gut microbiome through probiotics and a healthy diet may improve glymphatic system function and brain health, thereby preventing cognitive disorders.</p>