<p>Given the rising issue of antimicrobial resistance and the slow progress in the development of novel antibiotics, the identification of antimicrobial agents from ethnopharmacological plants has become a promising strategy. Baicalein is a flavonoid compound derived from medicinal plants with a wide range of pharmacological activities. It exhibits broad-spectrum antimicrobial activity against various clinically relevant bacteria and fungi in a dose-dependent manner. Moreover, baicalein suppresses the development of antimicrobial resistance, enhances the efficacy of conventional antibiotics, and converts their bacteriostatic effects into bactericidal activity. This highlights its potential as both an antimicrobial agent and an antibiotic adjuvant. This review systematically summarizes the antimicrobial properties of baicalein, both as a monotherapy and in combination therapy, focusing on its effects on planktonic and biofilm cells, as well as its beneficial actions <i>in vivo</i> infections. Moreover, we provide an in-depth analysis of the potential molecular targets of baicalein, including the cell membrane and cell wall, core metabolic processes, resistance mechanisms, and quorum sensing systems. We also discuss the limitations of current research and outline future research directions, emphasizing the need for high-quality studies to comprehensively evaluate the clinical efficacy and safety of baicalein in infection treatment. This review aims to offer new insights and recommendations for its future clinical translation.</p> Graphical abstract <p></p>