Cranberry is a fruit originally from New England and currently growing throughout the east and northeast parts of the USA and Canada. The supplementation of cranberry extracts as nutraceuticals showed to contribute to the prevention of urinary tract infections, and most likely it may help to prevent cardiovascular and gastroenteric diseases, as highlighted by several clinical trials. However, aiming to validate the efficacy and safety of clinical applications as long-term randomized clinical trials (RCTs), further investigations of the mechanisms of action are required. In addition, a real challenge for next years is the standardization of cranberry's polyphenolic fractions. In this context, the optimization of the extraction process and downstream processing represent a key point for a reliable active principle for the formulation of a food supplement. For this reason, new non-conventional extraction methods have been developed to improve the quality of the extracts and reduce the overall costs. The aim of this survey is to describe both technologies and processes for highly active cranberry extracts as well as the effects observed in clinical studies and the respective tolerability notes.