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<i>Saccharomyces cerevisiae</i> var. <i>boulardii</i> is best known for its treatment efficacy against different gastrointestinal diseases. This probiotic yeast can significantly protect the normal microbiota of the human gut and inhibit the pathogenicity of different diarrheal infections. Several clinical investigations have declared <i>S. cerevisiae</i> var. <i>boulardii</i> a biotherapeutic agent due to its antibacterial, antiviral, anti-carcinogenic, antioxidant, anti-inflammatory and immune-modulatory properties. Oral or intramuscular administration of <i>S. cerevisiae</i> var. <i>boulardii</i> can remarkably induce health-promoting effects in the host body. Different intrinsic and extrinsic factors are responsible for its efficacy against acute and chronic gut-associated diseases. This review will discuss the clinical and beneficial effects of <i>S. cerevisiae</i> var. <i>boulardii</i> in the treatment and prevention of different metabolic diseases and highlight some of its health-promising properties. This review article will provide fundamental insights for new avenues in the fields of biotherapeutics, antimicrobial resistance and one health.