Stevia rebaudiana Bertoni is a plant originating in Paraguay that is well-known for the sweet taste of its leaves. Stevia extract is widely used as a substitute for sucrose, it contains more than 10 compounds, called steviol glycosides (SGs), of which the best characterised are stevioside and rebaudioside A. All steviol glycosides need a bioactivation by intestinal bacteria, through which they are converted to steviol, the active metabolite. Indeed, the pharmacodynamic profile of stevia extract and steviol glycosides is related to steviol. A number of animal studies and clinical trials have been performed to investigate the effects of SGs, mostly of stevioside and rebaudioside A, observing that, beside the sweet taste, these natural derivatives may offer a multitude of beneficial effects on health. Indeed, growing evidence points to a nutraceutical use of Stevia rebaudiana Bertoni and its SGs. Moreover, an examination of toxicological profiles and adverse effects carried out from regulatory agencies in order to authorise its commercialisation as a sweetener has been here reported.