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The currently available anti-obesity therapies encounter many associated risks and side effects often causing the ineffectiveness of treatment. Therefore, various plant-derived substances have been extensively studied as a promising support or even an alternative for existing anti-obesity therapies. This review is dealing with the anti-obesity potential of edible and ethnomedicinal rhubarb species and emerging possible role of the rhubarb-derived extracts or individual compounds in the prevention of obesity and perspectives for their use in an anti-obesity treatment. A special emphasis is put on the most popular edible specimens, i.e., Rheum rhabarbarum L. (garden rhubarb) and Rheum rhaponticum L. (rhapontic rhubarb, Siberian rhubarb); however, the anti-obesity potential of other rhubarb species (e.g., R. officinale, R. palmatum, and R. emodi) is presented as well. The significance of rhubarb-derived extracts and low-molecular specialized rhubarb metabolites of diversified chemical background, e.g., anthraquinones and stilbenes, as potential modulators of human metabolism is highlighted, including the context of cardiovascular disease prevention. The available reports present multiple encouraging rhubarb properties starting from the anti-lipidemic action of rhubarb fibre or its use as purgative medicines, through various actions of rhubarb-derived extracts and their individual compounds: inhibition of enzymes of cholesterol and lipid metabolism, targeting of key molecular regulators of adipogenesis, regulators of cell energy metabolism, the ability to inhibit pro-inflammatory signalling pathways and to regulate glucose and lipid homeostasis contributing to overall in vivo and clinical anti-obesity effects. Full article