The detection of serum markers is important for the early diagnosis and monitoring of diseases, but conventional detection methods have the problem of low specificity or sensitivity. CRISPR/Cas13a-based biosensors have the characteristics of simple detection methods and high sensitivity, which have a certain potential to solve the problems of conventional detection. This paper focuses on the research progress of CRISPR/Cas13a-based biosensors in serum marker detection, introduces the principles and applications of fluorescence, electrochemistry, colorimetric, and other biosensors based on CRISPR/Cas13a in the detection of serum markers, compares and analyzes the differences between the above CRISPR/Cas13a-based biosensors, and looks forward to the future development direction of CRISPR/Cas13a-based biosensors.