Exosomes are 30-150 nm vesicles derived from diverse cell types, serving as one of the most important biomarkers for early diagnosis and prognosis of diseases. However, the conventional detection method for exosomes faces significant challenges, such as unsatisfactory sensitivity, complicated operation, and the requirement of complicated devices. In recent years, colorimetric exosome biosensors with a visual readout underwent rapid development due to the advances in natural enzyme-based assays and the integration of various types of nanozymes. These synthetic nanomaterials show unique physiochemical properties and catalytic abilities, enabling the construction of exosome colorimetric biosensors with novel principles. This review will illustrate the reaction mechanisms and properties of natural enzymes and nanozymes, followed by a detailed introduction of the recent advances in both types of enzyme-based colorimetric biosensors. A comparison between natural enzymes and nanozymes is made to provide insights into the research that improves the sensitivity and convenience of assays. Finally, the advantages, challenges, and future directions of enzymes as well as exosome colorimetric biosensors are highlighted, aiming at improving the overall performance from different approaches.