Purpose of Review <p>Artificial sweeteners (ASs) are widely used as sugar substitutes to reduce caloric intake. Emerging evidence indicates that these compounds are not metabolically inert and can alter gut microbiota composition and downstream metabolic regulation. </p> <p>This review synthesizes recent mechanistic and clinical evidence on how commonly used ASs—particularly sucralose, saccharin, acesulfame-K, aspartame, and steviol glycosides—modulate intestinal microbiota.</p> Recent Findings <p>Experimental and human studies show that AS exposure is associated with alterations in microbial diversity, short-chain fatty acid (SCFA) production, and gut barrier integrity. These alterations are linked to changes in glucose homeostasis, insulin sensitivity, and energy metabolism. </p> <p>Proposed mechanisms include modulation of nutrient-sensing G-protein-coupled receptors, interference with bile acid metabolism, and receptor-independent activation of intracellular signaling pathways such as PI3K/Akt and mTORC1. Notably, responses in human studies appear highly individualized and dose-dependent, highlighting substantial interindividual variability.</p> Summary <p>This review integrates microbiome, metabolic, and mechanistic perspectives to identify areas of emerging consensus, conflicting results, and critical research gaps in AS–microbiota–metabolism interactions. Current evidence suggests that ASs can modulate host metabolism through both microbiota-dependent and independent mechanisms. These findings have direct implications for clinical dietary guidance and risk stratification, particularly among individuals with obesity, insulin resistance, or other metabolic disorders.</p>