Nowadays, aptamer-based biosensors and electrochemical measurements represent one of the efficient tools for the detection of drugs in both medical and veterinary. Precise trace values analysis of chemicals, especially drugs, plays a crucial role in food and therapeutic safety evaluations that are often time-consuming and costly. Ultimately, accurate determination of therapeutic medications like antibiotics in food, environmental resources, and biological matrices is very important for protecting public health and drug monitoring (TDM) for effective treatment. This review highlights recent advancements in electrochemical aptasensors as an innovative approach offering high sensitivity, specificity, and rapid detection of clinical and veterinary drugs at lower costs. We provide a comprehensive overview of the advancements and discuss the challenges and prospects of electrochemical aptasensing in drug residue detection across various samples.