This study focused on maximizing the extraction yield of total phenolics and flavonoids from Curcuma Zedoaria leaves as a function of time (80–120 min), temperature (60–80 °C) and ethanol concentration (70–90 v/v%). The data were subjected to response surface methodology (RSM) and the results showed that the polynomial equations for all models were significant, did not show lack of fit, and presented adjusted determination coefficients (R 2) above 99%, proving their suitability for prediction purposes. Using desirability function, the optimum operating conditions to attain a higher extraction of phenolics and flavonoids was found to be 75 °C, 92 min of extraction time and 90:10 of ethanol concentration ratios. Under these optimal conditions, the experimental values for total phenolics and flavonoids of Curcuma zedoaria leaves were 125.75 ± 0.17 mg of gallic acid equivalents and 6.12 ± 0.23 mg quercetin/g of extract, which closely agreed with the predicted values. Besides, in this study, the leaves from Curcuma zedoaria could be considered to have the strong antioxidative ability and can be used in various cosmeceuticals or medicinal applications.