Proteins are vital components of living cells and the loss of their native functions has been associated with a wide variety of medical conditions. From this point of view, investigation of the protein microenvironment is crucial to support the development of therapeutic approaches capable of ensuring cellular functions. Therefore, analytical assays for the detection, quantification, and characterization of proteins, drugs, and protein-drug complexes play an essential role in fundamental research and clinical applications. Electrochemistry arises as an alternative methodology for fast assessment of proteins and drugs and is attractive due to the adaptability to miniaturization and scalability of electroanalytical devices, which then can be further employed as strategies towards personalized medical care. Thus, this review summarizes electrochemical investigations in the past 10 years on protein-based analytical devices and biosensors. A general overview of electrochemical assays that integrate proteins with nanostructured materials and conductive polymers is presented. Applications of electrochemical assays and biosensors were divided into four categories. First, those designed for drug screening strategies that focus on targeting specific intracellular, extracellular, or membrane protein subdomains to modulate their functions, aggregation/misfolding of proteins, and protein degradation pathways. Then, drug metabolism assays that involve mimicking natural metabolic pathways to identify potential safety and efficacy issues related to a drug or its metabolites. The third was dedicated to electrochemical drug delivery systems with anchored drugs in the form of bioconjugates, while the fourth was dedicated to electroanalytical methodologies for quantitative drug assays, where the electroactivity of the target species is often used to correlate the electrochemical signal to their concentration.