Optimization of extraction of antioxidative phenolic compounds from cashew (Anacardium occidentale L.) leaves was performed using response surface methodology (RSM). The central composite design (CCD) was used to establish treatments based on three independent variables, including extraction temperature, time, and ethanol-to-solid ratio. Total phenolic content (TPC), antioxidative activities (DPPH, ABTS radical scavenging activities, and FRAP), and % yield were monitored. The extraction yield was 8.64% under the following optimized condition: extraction at 34.7 degrees C for 64 min with an ethanol-to-solid ratio of 18:1 vol/wt. TPC was 564.60 mg GAE/g dry extract and DPPH, ABTS radical scavenging activities, and FRAP were 11.74, 5.56, and 8.11 mmol TE/g dry extract, respectively. The experiment values were in accordance with the predicted values. Isoquercetin, catechin, hydroquinin, gallic acid, tannic acid, and rutin were found in the extract. The extract could therefore be used as natural antioxidant for food application or as nutraceutical. Practical applicationsCashew leaf is a potential source of phenolics with antioxidative activity. Extraction method is the first important step in isolation of interested compound, in which the target compounds are extracted with high recovery and without interferences. Optimization of extraction is the procedure that can be used to extract the bioactive compounds having antioxidant capacity with high efficiency. Cashew leaf extract also can be used for food application or serve as nutraceuticals.