Abstract An efficient microwave-assisted extraction (MAE) technique was employed to extract total phenolics (TP) from sweetpotato [Ipomoea batatas (L.) Lam.] leaves (TPSL). The optimal conditions for microwave-assisted extraction of TPSL were determined by response surface methodology. A face-centered cubic design (FCD) was applied to evaluate the effects of three independent variables (microwave power, extraction time and ethanol proportion) on the recovery of TPSL. The correlation analysis of the mathematical-regression model indicated that quadratic polynomial model could be employed to optimize the microwave extraction of TPSL. From response surface plots, microwave power, extraction time and ethanol proportion exhibited independent and interactive effects on the extraction of TPSL. The optimal conditions to obtain the highest recovery of TPSL were as follows: microwave power, 302 W; extraction time, 123 s; ethanol proportion, 53% (v/v). Under these optimal conditions, the experimental values agreed with the predicted ones by analysis of variance. It indicated high fitness of the model used and the success of response surface methodology for optimizing TPSL extraction. After method development, the antioxidant activity of the MAE extract was preliminarily evaluated. MAE showed obvious advantages in terms of high extraction efficiency and antioxidant activity of extract with in shortest extraction time. Industrial Relevance: Sweet potato leaves have been neglected except for a partial use as livestock feed in China. This study describes the response surface optimization of microwave-assisted extraction (MAE) process for the enhanced recovery of total phenolics from sweetpotato leaves (TPSL). MAE showed obvious advantages in terms of high extraction efficiency and antioxidant activity of extract within shortest extraction time. TPSL obtained using MAE showed potential for use in health-care food and pharmaceutical industry.