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Chronic kidney disease (CKD) represents a significant public health problem. Patients with CKD have high morbidity and mortality, mainly due to cardiovascular diseases. As CKD progresses, impaired renal clearance leads to the progressive accumulation of uremic toxins, culminating in deleterious effects on multiple organ systems. Uremic toxins contribute to cardiovascular disease by inducing inflammation, oxidative stress, and endothelial barrier dysfunction, thereby promoting atherosclerotic processes. They are also potentially implicated in neurological impairment, bone disorders, and sarcopenia. Some uremic toxins originate from dietary components and gut microbiota metabolism, which are key mechanisms and pathways in uremic toxicity. Current dialysis therapies only partially mitigate uremic toxicity, highlighting the need for strategies that reduce uremic toxin generation as well as more efficient dialysis modalities. Given the importance of uremic toxins in CKD progression, this review provides a comprehensive overview of uremic toxicity, focusing on its pathophysiological mechanisms, its relationship with the gut microbiota, and emerging interventions to mitigate its deleterious effects.