Hibiscus sabdariffa Linn. Malvaceae (HS) is characterized by its edible calyxes. The HS calyxes are widely used for cosmetic, food, and medicinal applications. According to ethnobotanical evidence, decoction, infusion, or maceration extracts from HS calyxes have been used in folk medicine to treat many ailments. Moreover, several in vitro and in vivo studies have demonstrated the pharmacological properties and potential human health benefits of HS consumption. On the other hand, the evaluation of the physiological effects and health benefits of HS in clinical studies is most challenging. Therefore, this narrative review summarizes and discusses the physiological effects and health benefits of HS calyxes reported in clinical trials. Preparations obtained from HS calyxes (extracts, infusions, decoction, teas, beverages, capsules, and pills) are used as non-pharmacological therapies to prevent/control diverse chronic non-communicable diseases. The most-reported HS health benefits are its antihypertensive, antidyslipidemic, hypoglycemic, body fat mass reduction, nephroprotective, antianemic, antioxidant, anti-inflammatory, and anti-xerostomic activities; these effects are associated with the phytochemicals found in HS. Moreover, no adverse effects were reported during the clinical trials. However, clinical studies exhibited some limitations; thus, further studies are required to validate the clinical efficacy of HS in large-scale studies with higher doses and a good experimental design