Drug abuse is seriously endangering human health and jeopardizing society. There is an urgent need for rapid, sensitive, portable, and easy-to-operate methods for the daily detection of drugs in biological matrices. However, current drug detection methods based on chromatography, spectroscopy, immunosorbent assays, etc. are limited by the requirements of high logistical instruments and laboratory. Herein, we proposed a wearable electrochemical aptasensor with high sensitivity and specificity for the direct capture and rapid detection of multiple drugs in sweat. The single aptamer and dual aptamers with different base compositions were designed to compose the aptasensor array. Molecular docking simulations demonstrated different binding affinities between bioamines and aptamers. The developed aptasensor array is shown to be sufficient to generate distinct electrochemical fingerprints for different psychoactive drugs and interfering substances by extracting variable features from electrochemical signals. Sixteen analytes in the same concentration or gradient concentrations were identified with 100% accuracy. In addition, the wearable sensor platform was demonstrated to discriminate various drugs with similar chemical structures in artificial sweat and human sweat samples. The sensor array not only provided a new rapid method for the detection of drugs but also served as a reference for developing wearable sensors for onsite and daily testing of human biochemical information.