Mitochondrial dysfunction is observed in a broad range of human diseases, including rare genetic disorders and complex acquired pathologies. For this reason, there is increasing interest in identifying safe and effective strategies to mitigate mitochondrial impairments. Natural compounds are widely used for multiple indications, and their broad healing properties suggest that several may improve mitochondrial function. This review focuses on (-)-epicatechin, a monomeric flavanol, and its effects on mitochondria. The review summarizes the available data on the effects of acute and chronic (-)-epicatechin supplementation on mitochondrial function, outlines the potential mechanisms involved in mitochondrial biogenesis induced by (-)-epicatechin supplementation and discusses some future therapeutic applications.