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Honey has been recognized for its medicinal properties for centuries, with well-documented benefits such as antibacterial, anti-inflammatory, and antioxidant activities. However, despite the widespread use of honey for health-related purposes, many of the underlying mechanisms responsible for its bioactivity remain underexplored. This review delves into the complexity of honey's composition, particularly focusing on the active substances and the honey microbiota contribution to its properties. We aim to bridge the gap in understanding how honey's multifaceted bioactivity arises from interactions between bees, plants, and microorganisms. The review sheds light on the key compounds, including hydrogen peroxide, methylglyoxal, polyphenols, and antimicrobial peptides, which play vital roles in honey's health benefits. It also highlights the often-overlooked contributions of the honeybee's gut microbiota and the nectar's microbiota, which together influence the chemical transformation of nectar into honey and enhance its therapeutic efficacy. By examining the current literature, this article emphasizes the need for deeper investigation into how various factors-such as floral origin, bee subspecies, and environmental conditions-affect the medicinal quality of honey. Understanding these mechanisms could lead to optimized use of honey in medical applications and reveal new therapeutic potentials. This article provides a comprehensive review of the intricate processes and components that make honey not only a nutritional food source but also a potent natural medicine. [ABSTRACT FROM AUTHOR]