Natural hydrophobic deep eutectic solvents (NaHDESs), composed of natural components like menthol, fatty acids, and organic acids, are sustainable alternatives to conventional solvents for extracting carotenoids from agro-industrial by-products. This study assessed the performance of nine NaHDESs for extracting β-carotene from pumpkin peels, identifying DL-menthol/lactic acid (1:2) as the most effective solvent, achieving a yield of 0.823 ± 0.019 mg/mL of β-carotene, corresponding to 93.95% of the yield obtained using acetone. Optimization through Box-Behnken design (BBD) and response surface methodology (RSM) established ideal extraction conditions: a molar ratio of HBA:HBD at 1:4, a solvent-to-sample ratio of 26:1, and an extraction time of 30 min. These conditions maximized β-carotene recovery while minimizing energy consumption and process costs. Using NaHDESs facilitates the valorization of food waste, achieving extraction efficiencies of up to 25.05% of the theoretical carotenoid content in pumpkin peels. Their high performance and environmentally friendly profile underscore the potential of NaHDESs as sustainable alternatives to conventional solvents.