Background Beetroot (Beta vulgaris L.) is a rich source of health-promoting bioactive compounds, including betalains, phenolic compounds and dietary nitrates. However, the practical applications of these compounds are limited by their inherent chemical instability and poor systemic bioavailability. Scope and approach This study critically examines fermentation as a targeted biotechnological strategy to overcome these limitations. It systematically connects the microbial and enzymatic biotransformations of beetroot's key bioactives to the modulation of its health-promoting properties. The review also elucidates the underlying molecular mechanisms, including the regulation of key signaling pathways, examines the landscape of novel fermented beetroot products, and evaluates preclinical findings within the broader context of industrial applications. Key findings and conclusions Fermentation creates an acidic environment that enhances betalains stability, whereas microbial enzymes improve the bioaccessibility of phenolic compounds. These transformations increase the therapeutic potential of beetroot, notably its antioxidant and anti-inflammatory effects, by modulating Nuclear factor erythroid 2–related factor 2/Heme oxygenase-1 (Nrf2/HO-1) and Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways. While preclinical studies have demonstrated strong anticancer activity, a significant translational gap exists due to poor bioavailability and a lack of human clinical trials. Fermentation effectively transforms beetroot into a valuable functional ingredient for novel foods, such as probiotic beverages and synbiotic yogurt. However, optimizing and standardizing fermentation processes to ensure safety, consistency, and viable probiotic counts remains a critical challenge for successful commercialization.