This study investigates the effects of extraction parameters, including temperature, time, solvent type, ethanol concentration, and solvent-to-material ratio, on the extraction efficiency of phenolic and flavonoid compounds from durian peels. Ethanol and water were utilized as solvents to evaluate their efficacy, and the antioxidant activity of the extracts was determined using the DPPH radical scavenging assay. Results revealed that ethanol extracts achieved superior phenolic and flavonoid yields and stronger antioxidant activity, with an IC50 value of 68.61 µg/mL compared to 82.68 µg/mL for water extracts. Optimal conditions for phenolic and flavonoid extraction were identified at 80°C and 15 minutes for both solvents, while 70% ethanol at a 30:1 solvent-to-material ratio demonstrated the highest extraction efficiency. The findings suggest that water can serve as a sustainable alternative to ethanol, offering an environmentally friendly and cost-effective option for bioactive compound extraction. This study highlights the potential of valorizing durian peels as a source of natural antioxidants for pharmaceutical, cosmetic, and food applications.