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The biocompatibility of Magnesium-based materials (MBMs) is critical to the safety of biodegradable medical devices. As a promising metallic biomaterial for medical devices, the issue of greatest concern is devices’ safety as degrading products are possibly interacting with local tissue during complete degradation. The aim of this review is to summarize the biological responses to MBMs at the cellular/molecular level, including cell adhesion, transportation signaling, immune response, and tissue growth during the complex degradation process. We review the influence of MBMs on gene/protein biosynthesis and expression at the site of implantation, as well as throughout the body. This paper provides a systematic review of the cellular/molecular behavior of local tissue on the response to Mg degradation, which may facilitate a better prediction of long-term degradation and the safe use of magnesium-based implants through metal innovation