The poor corrosion resistance of magnesium (Mg) alloys significantly restricts their wide applications. The preparation of a layered double hydroxides (LDHs) film can provide effective corrosion protection for Mg alloys. Nevertheless, research on the effect of the Mg alloy microstructure on LDHs film growth is paid less attention, which was studied in detail in this work. Herein, a Mg-2Zn-xMn alloy with different Mn contents was produced, and an LDHs film was then synthesized on their surfaces. The addition of Mn causes a different microstructure in the Mg-2Zn-xMn alloy, which is gradually refined with increasing Mn content, further affecting the surface morphology, surface chemistry, and corrosion protection of the LDHs film. When the Mn content is 1 wt.% (x = 1), the LDHs film presents the best corrosion protection, with the lowest corrosion current density. No obvious corrosion product could be observed by the naked eyes on the surface. By contrast, severe corrosion occurs on the Mg-2Zn-0Mn alloy (x = 0). Finally, the LDHs film growth mechanism was proposed.