Chestnut peels are a poorly characterized, underexploited by-product of the agri-food industry. This raw material is rich in bioactive compounds, primarily polyphenols and tannins, that can be extracted using different green technologies. Scaling up the process for industrial production is a fundamental step for the valorization of the extract. In this study, subcritical water extraction was investigated to maximize the extraction yield and polyphenol content. Lab-scale procedures have been scaled up to the semi-industrial level as well as the downstream processes, namely, concentration and spray drying. The extract antioxidant capacity was tested using in vitro and cellular assays as well as a preliminary evaluation of its antiadipogenic activity. The temperature, extraction time, and water/solid ratio were optimized, and the extract obtained under these conditions displayed a strong antioxidant capacity both in in vitro and cellular tests. Encouraging data on the adipocyte model showed the influence of chestnut extracts on adipocyte maturation and the consequent potential antiadipogenic activity. Chestnut peel extracts characterized by strong antioxidant power and potential antiadipogenic activity were efficiently obtained by removing organic solvents. These results prompted further studies on fraction enrichment by ultra- and nanofiltration. The semi-industrial eco-friendly extraction process and downstream benefits reported here may open the door to production and commercialization.