<![CDATA[Euphorbia hirta is a medicinal plant containing phenolic compounds with potential antioxidant and pharmacological activities. The efficiency of phenolic compound extraction is strongly influenced by extraction conditions, particularly solvent concentration, solvent-to-solid ratio, and extraction time. This study aimed to evaluate the effects of ethanol concentration, solvent-to-solid ratio, and ultrasonic extraction time on the total phenolic content (TPC) of Euphorbia hirta leaves. Ultrasonic-assisted extraction was optimized using a Box–Behnken design with three independent variables: solvent-to-solid ratio (5–15 g/mL), ethanol concentration (50–96%), and extraction time (5–15 min). Total phenolic content was determined using the Folin–Ciocalteu method and expressed as mg gallic acid equivalent (GAE) per gram of extract. Based on the simulated experimental data, TPC values ranged from 166.82 ± 1.62 to 206.17 ± 1.18 mg GAE/g extract. The highest TPC was obtained at a solvent-to-solid ratio of 10 g/mL, ethanol concentration of 73%, and extraction time of 10 min, with a TPC of 206.17 ± 1.18 mg GAE/g extract. The results indicate that extraction conditions significantly influence the recovery of phenolic compounds from E. hirta leaves. The application of ultrasonic-assisted extraction combined with Box–Behnken design provides an effective approach for optimizing phenolic compound extraction from E. hirta..]]>
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