Cynara cardunculus L. (cardoon), a versatile perennial crop, thrives in challenging environments with high productivity. Its flowers are valued for their coagulating properties in cheesemaking, while its leaves, rich in bioactive compounds, are normally discarded. This study assessed the antioxidant and antimicrobial potential of ethanolic and methanolic extracts from fresh and dried cultivated cardoon var. Altilis DC leaves to evaluate the impact of oven-drying with forced air circulation on the bioactive profile of the leaves. Dried cultivated cardoon leaf extracts exhibited stronger antioxidant activity than fresh leaf extracts, although fresh leaves contained more polyphenolic compounds. Among the 16 identified compounds, chlorogenic acid, apigenin, and luteolin were the most abundant. The best antioxidant activity was observed in dried leaf extracts prepared with both methanol and ethanol solvents. Regarding antimicrobial properties, Gram-positive bacteria were more sensitive to the extracts than Gram-negative bacteria. The dried leaf ethanolic extract demonstrated the strongest antibacterial activity, with lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. However, only mild inhibition was observed against Aspergillus fumigatus. The findings indicate dried cardoon leaves as a valuable by-product rich in bioactive compounds with potential applications in the food, cosmetic, and pharmaceutical industries. The use of active compounds obtained from cardoon leaves is aligned with the concepts of circular economy and sustainability. This approach promotes both environmental and economic sustainability by transforming high-value by-products into innovative applications.