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Abstract Background Besides fibre production, Corchorus olitorius is considered a nutritional and medicinal plant in traditional medicine. Its leaves possess different antioxidant compounds and display various biological properties. This study optimized the ultrasound-assisted extraction (UAE) parameters like temperature, time, solvent concentration, and liquid–solid ratio for total flavonoids (TFC) and total polyphenols content (TPC) from leaves employing response surface methodology (RSM). Results Findings demonstrated that under the optimized conditions, the highest extraction yield of total flavonoids (7.17 mg QE/g DW) and total polyphenol content (13.92 mg GAE/g DW) were recorded with the ethanol concentration 70.92%, temperature 68.06 °C, liquid–solid ratio 48.80 mL/mg, and ultrasound irradiation time 37.20 min. The optimum value of TFC (6.96 mg QE/g DW) and TPC (13.38 mg GAE/g DW) from the experiment of verification of optimized conditions was close to the predicted value and significantly superior to the conventional heat reflux extraction (HRE). LC–MS and HPLC analysis of the optimized extract from UAE demonstrated the existence of six major phenolic compounds, including chlorogenic acid, isoquercetin, hyperoside, adhyperforin, 1,3-di-O-caffeoylquinic acid, and 3,4-di-O-caffeoylquinic acid. Furthermore, the antioxidant test of the UAE leaves extract revealed an excellent 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•) and hydroxyl radical scavenging with IC50 values of 226.29, 199.53 and 402.02 µg/mL, respectively, compared to HRE with 336.31 µg/mL, 253.86 µg/mL, 520.08 µg/mL. Conclusions The developed optimization method could contribute to the good recovery of natural antioxidants from C. olitorius in the pharmaceuticals and food industries. Graphical Abstract |