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A global epidemiological shift has been observed in recent decades, characterized by an increase in age-related disorders, notably non-communicable chronic diseases, such as type 2 diabetes mellitus, cardiovascular and neurodegenerative diseases, and cancer. An appreciable causal link between changes in the gut microbiota and the onset of these maladies has been recognized, offering an avenue for effective management. Kefir, a probiotic-enriched fermented food, has gained significance in this setting due to its promising resource for the development of functional or value-added food formulations and its ability to reshape gut microbial composition. This has led to increasing commercial interest worldwide as it presents a natural beverage replete with health-promoting microbes and several bioactive compounds. Given the substantial role of the gut microbiota in human health and the etiology of several diseases, we conducted a comprehensive synthesis covering a total of 33 investigations involving experimental animal models, aimed to elucidate the regulatory influence of bioactive compounds present in kefir on gut microbiota and their potential in promoting optimal health. This review underscores the outstanding nutritional properties of kefir as a central repository of bioactive compounds encompassing micronutrients and amino acids and delineates their regulatory effects at deficient, adequate, and supra-nutritional intakes on the gut microbiota and their broader physiological consequences. Furthermore, an investigation of putative mechanisms that govern the regulatory effects of kefir on the gut microbiota and its connections with various human diseases was discussed, along with potential applications in the food industry.