Small biomolecules play a critical role in the fundamental processes that sustain life and are essential for the proper functioning of the human body. The detection of small biomolecules has garnered significant interest in various fields, including disease diagnosis and medicine. Electrochemical techniques are commonly employed in the detection of critical biomolecules through the principle of redox reactions. It is also a very convenient, cheap, simple, fast, and accurate measurement method in analytical chemistry. Zeolitic imidazolate frameworks (ZIFs) are a unique type of metal-organic framework (MOF) composed of porous crystals with extended three-dimensional structures. These frameworks are made up of metal ions and imidazolate linkers, which form a highly porous and stable structure. In addition to their many advantages in other applications, ZIFs have emerged as promising candidates for electrochemical sensors. Their large surface area, pore diameter, and stability make them ideal for use in sensing applications, particularly in the detection of small molecules and ions. This review summarizes the critical role of small biomolecules in the human body, the standard features of electrochemical analysis, and the utilization of various types of ZIF materials (including carbon composites, metal-based composites, ZIF polymer materials, and ZIF-derived materials) for the detection of important small biomolecules in human body fluids. Lastly, we provide an overview of the current status, challenges, and future outlook for research on ZIF materials.