Optimal heating conditions for Citrus sunki Hort. Tanaka peel (CP) were obtained by using the response surface methodology (RSM) to enhance the alcohol metabolic enzyme activity of the CP extract. Heating temperature and time were independent variables, while alcohol dehydrogenase (ADH) activity, acetaldehyde dehydrogenase (ALDH) activity, DPPH radical scavenging activity, total flavonoid contents (TFC), and total phenol contents (TPC) of the extracts were dependent variables. With 11 conditions as specified by the RSM, the acquired optimal heating temperature and time were 144.8°C and 50.2 min, respectively. ADH activity, ALDH activity, DPPH radical scavenging activity, TFC, and TPC of the CP extract prepared under optimal conditions were predicted to be 250.27%, 216.55%, 85.58%, 0.132 mg QE/mL, and 3.153 mg GAE/mL, respectively. Under optimum conditions, the experimental and predicted values showed excellent reproducibility within the 95% confidence interval. This is the first report on the alcohol metabolic enzyme activity of CP extract, and these optimum heating conditions for CP can support the development of functional foods for overcoming a hangover.