The aging of our population is accompanied by an increased prevalence of chronic diseases. Among those, liver, joint and adipose tissue-related pathologies have a major socio-economic impact. They share common origins as they result from a dysregulation of the inflammatory and metabolic status. Plant-derived nutrients and especially polyphenols, exert a large range of beneficial effects in the prevention of chronic diseases but require clinically validated approaches for optimized care management. In this study, we designed an innovative clinical approach considering the metabolites produced by the digestive tract following the ingestion of an artichoke leaf extract. Human serum, enriched with metabolites deriving from the extract, was collected and incubated with human hepatocytes, human primary chondrocytes and adipocytes to determine the biological activity of the extract. Changes in cellular behavior demonstrated that the artichoke leaf extract protects hepatocytes from lipotoxic stress, prevents adipocytes differentiation and hyperplasia, and exerts chondroprotective properties in an inflammatory context. These data validate the beneficial health properties of an artichoke leaf extract at the clinical level and provide both insights and further evidence that plant-derived nutrients and especially polyphenols from artichoke may represent a relevant alternative for nutritional strategies addressing chronic disease issues.