Natural product is an important source of small-molecule drugs and probes, but its synthesis is challenging and has attracted lasting attention in the field of organic chemistry. With the continuous advancement of chromatographic techniques for separation and spectroscopic methods for structural analysis, the pace of discovering tiny bioactive natural products is accelerating, concomitantly leading to an increase in the diversity and complexity of the newly identified structures. However, to meet the demand of the quantity for the study of their structure-activity relationships, target identification, in vivo activity evaluation, etc., growing challenges in the requirement for the synthetic efficiency, economy, and scalability of natural products are emerging. Synthetic practices in a chemoenzymatic way have provided multi-dimensional visions for natural product research, which emerged as a hot research topic in recent years. On the one hand, enzymatic catalysis has provided highly efficient and selective synthetic methodologies that would complement traditional synthetic methods. On the other hand, the introduction of enzyme-catalyzed reactions would bring a new mode of strategic design for synthesis, enabling the rapid and diverse synthesis of natural products with high efficiency. In this context, how to integrate the enzyme-catalyzed reactions into the synthesis of natural products is the key to a successful chemoenzymatic synthesis. We herein summarized three roles played by the applications of enzyme-catalyzed reactions in the current practices of chemoenzymatic synthesis of natural products. ①The involvement of biocatalysis would introduce a chiral center or a key functional group into the starting material, or supply complex synthetic precursors (e.g., polysubstituted (hetero)aromatics, chiral pools, etc.) via in vitro enzyme-catalyzed reactions or fermentation, hence advancing the starting line of synthesis; ②Late-stage enzyme-catalyzed chemo-, regio-, and stereoselective modifications of substrates with heavily substituted functional groups or inert positions of complex skeletons; ③The strategic application of enzymatic catalysis as a key carbon-carbon bond-forming step in the construction of the skeleton of natural product. Finally, we have also discussed the current challenges and future trends of the chemoenzymatic synthesis of natural products in three facets, including the design of synthetic strategy, the development of synthetic methods, as well as persons involved in the research. Thus, the integration of interdisciplinary methods and technologies, including chemical synthesis and biocatalysis, would invigorate the synthesis of natural products.