Honey is a nutritious, healthy, and natural food, to which antioxidant, anti-inflammatory, and antimicrobial properties have been attributed, mainly due to its content of phenolic compounds. The aim of this review is to analyze the available evidence of the effect of honey on humans. Forty-eight clinical trials published between 1985 and 2022 were analyzed, with a total of 3655 subjects. More beneficial effects of honey intake than no or negative effects on different cardiovascular and metabolic risk factors, glucose tolerance, mucositis caused by chemo-radiotherapy, cough in children and wound healing, among others have been observed. Although the number of studies conducted to date is limited and the different investigations are not standardized, beneficial effects of honey intake have been observed, especially when its intake replaces the intake of other sweeteners. In addition, honey could be a safe adjuvant to be administered alongside drugs used for certain diseases.