Humans continuously interact with physical, chemical, and biological environments that influence their health, safety, and quality of life. Sensing devices, such as electrochemical sensors that translate environmental qualities into electrical signals, are crucial for detecting biomarker concentrations in various biofluids. However, the understanding of electrochemical sensing is often incomplete, necessitating further study of chemical reactions and sensor‐electrode interactions for healthcare applications. This review analyzes crucial topics in chemical reactions in electrochemical sensing environments. First, the dynamics of chemical energy, the roles of acidic and alkaline fluids, chemical reaction tendencies, thermodynamic equilibria, Gibbs free energy, water dissociation, and the pH scale are discussed. Sensor materials or biomarkers undergo oxidation and reduction reactions in electrochemical sensing. Oxygen‐derived radicals and nonradical reactive species significantly influence biochemical reactions, cellular responses, and clinical outcomes. Then, the review delves into the impact of oxidation reduction reactions on human pathophysiology, redox reactions in hemoglobin, redox environments in human serum albumin and cells/tissues, and thermodynamics of biological redox reactions. Finally, recent advances in electrochemical techniques are presented and research challenges and future perspectives in electrochemical sensing for health applications are addressed.