The residue from pruning Cudrania tricuspidata trees is considered a rich source of energy and bioactive compounds. Recovering these compounds from C. tricuspidata tree pruning could help mitigate potential economic and environmental concerns. The primary aim of this study was to investigate the impact of extraction temperature, duration, and liquid-to- residue ratio on the antioxidant activity, total phenolic content, and total flavonoid content of C. tricuspidata tree pruning, using the response surface methodology. The results indicated that the microwave-assisted extraction temperature or microwave-assisted extraction time was the most crucial variable in the extraction process (Significance at p-value < 0.001- 0.05 for antioxidant activity and chemical profile). It is worth mentioning that the optimal extraction conditions for achieving maximum 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, 2,2'azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation induction activity, total polyphenol content, and total flavonoid content were distinct from one another, necessitating specific optimization for each targeted characteristic. The optimized extraction conditions yielded 85.8% DPPH radical scavenging activity, 95.4% ABTS radical cation induction activity, 2.72 mg/g total polyphenol content, and 2.53 mg/g total flavonoid content. These results highlight the potential of C. tricuspidata as a valuable dietary source of phenolic antioxidants for human health.