Small biomolecules in the human body have important effects on the health of the living body. Some of them are involved in the blood circulation and immune system of the living body Therefore, the detection of small molecules in living organisms in the study of small molecules in the physiological function of life is of great significance. Fourier Transform Surface Plasmon Resonance (FT-SPR) spectroscopy has been widely used in molecular detection in recent years due to its advantages of simple operation, high sensitivity, few samples required and real-time detection But for different molecules, especially those with very small molecular weight, FT-SPR direct detection has some disadvantages, such as unstable signal and low sensitivity. Therefore, a series of SPR small molecule sensors can be constructed for different detection targets to remedy the above shortcomings. In this paper, the research progress in the detection of small molecules by SPR technology is reviewed from the aspects of immunosensor (direct detection, Sandwich detection, competitive detection and inhibition detection), SPR molecular imprinting sensor and other SPR based sensors. The prospect of its development is also given.