AbstractIn this study, a pioneering cascade method involving ultrasound-assisted extraction (UAE) and Box–Behnken Design (BBD) was optimized to valorize pineapple core waste by the sequential extraction of, firstly phenolic compounds and, secondly, carotenoids. The effectiveness of the extraction was evaluated based on total polyphenol content (TPC) and antioxidant activity using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assays. Characterization of the carotenoids was performed using high-performance liquid chromatography with a diode array detector (HPLC–DAD). The initial characterization of dry pineapple core (DPC) samples revealed their nutritional composition, including protein, lipid, and carbohydrate weight percentages of 1.20 ± 0.05%, 5.3 ± 0.4%, and 88.6 ± 0.5%, respectively. The high extractives content (40.0 ± 4.5%) suggests a substantial presence of phenolic compounds, making the pineapple core a valuable source of natural antioxidants. The optimal UAE conditions for phenolic compound extraction were 70% amplitude, 5 min extraction time, and 2 cycles, yielding an antioxidant extract rich in phenolic compounds with a desirability value of 81.2%. Therefore, DPC was considered a valuable source of natural antioxidants. The extraction of β-carotene also showed promising results with optimal UAE conditions of 20% amplitude, 3 min extraction time, and 2 cycles. This research promotes the sustainable use of pineapple waste and demonstrates the potential to obtain valuable additives for the food, pharmaceutical, and cosmetic industries, encouraging a more circular and efficient use of resources in the pineapple processing industry.