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In this study, a simple electrochemical sensor based on l -arginine membrane (P-L-arg/GCE) was developed for rapid and sensitive detection of MDMA and MDA. A polyarginine membrane was obtained through one-step direct electropolymerization, which provides more reaction sites for the analyte and improves the sensitivity of the sensor. Following the optimized selection parameters, the MDMA detection range was established at 1.0 × 10−7∼3.5 × 10−5 mol L−1, with a detection limit of 3.3 × 10−8 mol L−1. Similarly, the detection range for MDA was established at 1.0 × 10−7∼5.3 × 10−5 mol L−1 with a detection limit of 3.3 × 10−8 mol L−1. Additionally, the potential oxidation mechanism of MDMA and MDA during the REDOX process was analyzed by cyclic voltammetry. Furthermore, the proposed sensor exhibited superior selectivity, excellent reproducibility, and satisfactory stability. The proposed sensors can be used for reliable monitoring of MDMA or MDA in human urine and hair samples, respectively, and it has acceptable analytical reliability and enormous potential for practical applications. A simple and highly sensitive electrochemical technique has been developed to quantitatively detect MDMA and MDA using P-L-arg/GCE. By means of this sensor, the electrochemical characteristics of both analytes were thoroughly investigated. The sensor demonstrates sound selectivity, repeatability, and long-term stability in the detection of MDMA and MDA. Furthermore, the method can be applied to the determination of MDMA and MDA in human urine and blood samples. [Display omitted] • A high-sensitive sensor for trace detection of ecstasy was designed. • The possible mechanisms of MDMA and MDA were deduced. • The sensor exhibited a wide detection range and low detection limit. • The sensor was successfully applied to the detection of MDMA and MDA in human serum. [ABSTRACT FROM AUTHOR]