For centuries, honey, the main bee-hive product, has been widely used as an effective therapeutic agent against several health disorders, in addition to its extensive uses as a natural-healthy and energetic food. Further, bee-honey is a beneficial substance when we explore the many uses in medicine, including bacteria-and-virus killing such as Covid-19, body-protecting chemicals, anti-inflammatory, antioxidant, and anti-cancer activities. Honey is characterized by complex and variable chemical compositions depending on several fac-tors; botanical origin, climatic condition, bee health, and other stress factors, in particular, uncontrolled use of pesticides and adulteration in this product. Additionally, honey contains an important number of bioactive compounds (carbohydrates, lipids, amino acids, proteins, vitamins, and minerals) whose main roles are involved in medical therapies and wound healing. Thus, this review summarizes the literature about the chemical composition, biological activity, and factors affecting bee-honey production and quality.