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The intricate mechanisms governing brain health and function have long been subjects of extensive investigation. Recent research has shed light on two pivotal systems, the glymphatic system and the endocannabinoid system, and their profound role within the central nervous system. The glymphatic system is a recently discovered waste clearance system within the brain that facilitates the efficient removal of toxic waste products and metabolites from the central nervous system. It relies on the unique properties of the brain's extracellular space and is primarily driven by cerebrospinal fluid and glial cells. Conversely, the endocannabinoid system, a multifaceted signaling network, is intricately involved in diverse physiological processes and has been associated with modulating synaptic plasticity, nociception, affective states, appetite regulation, and immune responses. This scientific review delves into the intricate interconnections between these two systems, exploring their combined influence on brain health and disease. By elucidating the synergistic effects of glymphatic function and endocannabinoid signaling, this review aims to deepen our understanding of their implications for neurological disorders, immune responses, and cognitive well-being.