Along the way, investigations over the past few years have focused on developing new Zn-based alloys as future materials for medical implants due to the poor mechanical and degradation properties. Effective grain size control is a fundamental property of Zn-based alloys that has a significant impact on their mechanical properties and degradation rate through various methodical adjustments of the microstructure. In particular, these critical properties of Zn-based alloys largely depend on grains' size and distribution in the respective microstructures. The review article critically analyzes the influence of grain refinement and microstructure on the mechanical properties, biodegradability, and biocompatibility of Zn-based alloys. The article establishes the interdependence between microstructure, mechanical properties, degradation rate, and biocompatibility of both Zn and its alloys. We conclude integration of alloying and fabrication techniques can significantly control grain refinement in Zn-based alloys, and the use of innovative techniques such as dynamic recrystallization and inoculation can further improve the grain refinement process.