Valorization of Chestnut By-Products: Extraction, Bioactivity, and Applications of Shells, Spiny Burs, and Leaves

The European chestnut (<i>Castanea sativa</i> Mill.) industry generates substantial amounts of underutilized biomass, including shells, leaves, and spiny burs. Distinguishing itself from existing literature, this review presents a novel, integrated life-science analysis that redefines these by-products as a complementary 'bioactive triad', ranging from metabolic regulators to anti-virulence agents, rather than interchangeable sources of polyphenols. Although traditionally discarded, these by-products are rich sources of polyphenols, ellagitannins, and flavonoids, with promising potential for nutraceutical, cosmetic, and pharmaceutical applications. This review examines recent advances in the valorization of chestnut by-products, focusing on extraction strategies, chemical profiles, and biological activities. Shell valorization has increasingly shifted toward green extraction technologies, such as subcritical water extraction and deep eutectic solvents, which strongly influence bioactive recovery and composition. Chestnut leaves emerge as a sustainable resource enriched in hydrolysable tannins with anti-inflammatory and quorum sensing-inhibitory properties, particularly relevant for dermatological applications. Spiny burs, often the most phenolic-rich fraction, display marked antioxidant activity and the ability to potentiate conventional antibiotics against pathogens such as <i>Helicobacter pylori</i>. Despite these promising features, major challenges remain, including cultivar-dependent chemical variability, the predominance of in vitro evidence, and safety concerns related to the accumulation of potentially toxic elements. Overall, while chestnut by-products represent valuable resources within circular bioeconomy frameworks, their successful industrial and practical translation will require standardized extraction protocols, robust bioavailability assessments, and well-designed in vivo and clinical studies to ensure safety and efficacy.