Abstract: The present disclosure provides a chitosan-Fe coating-based synbiotic microcapsule with gastric acid resistance and intestinal targeted release and a preparation method thereof. The preparation method includes the following steps: preparation of mixed probiotics, preparation of a chitosan-Fe coating, preparation of a microcapsule, and freeze-drying. In the present disclosure, live probiotics wrapped in the microcapsule can avoid a weak acid resistance and a poor long-term storage stability of the probiotics; chitosan-Fe added to a wall material can significantly improve an embedding rate of the microcapsule, and can also achieve targeted release of the probiotics in the intestinal tract.