Previous work indicated that long-period stacking ordered (LPSO) phase and/or γʹ in rare earth containing Mg biomaterials had contradictory mechanisms responsible for their degradation in less complex or standard salt media, such as 0.9 % NaCl solution. They needed to be further investigated in a more realistic simulated body fluid (SBF). The present work investigated the influence of the amount and types of intermetallics on the degradation behavior of as-cast Mg-xDy-Zn (x = 5, 10, 15 wt.%) alloys using immersion test in Dulbecco’s modified Eagle’s medium (DMEM) + Glutamax together with 10 % Fetal bovine serum (FBS) under cell culture conditions. It was revealed that the existence of intermetallics exhibited different effects on the degradation behavior of alloys. At the early stage of immersion, Mg-10Dy-1.5Zn alloy suffered the most serious degradation among these three alloys, owing to its more severe micro galvanic corrosion. With the immersion proceeding, the degradation rate of Mg-5Dy-1.5Zn alloy consistently increased because of the scattered distribution of few intermetallics. In contrast, the continuous network structure of intermetallics and a compact degradation layer provided protection from further degradation for Mg-10Dy-1.5Zn and Mg-15Dy-1.5Zn alloys. In the as-cast Mg-5Dy-1.5Zn alloy, only small amount of intermetallics composed of W, γʹ and 18R LPSO phases acted as galvanic cathodes, accelerating its degradation. With Dy content increasing to 10 and 15 wt.%, large amounts of intermetallics including 18R LPSO and dense γʹ phases were formed, which on the other hand can serve as a continuous network barrier to retard degradation propagation. Finally, the good adhesion and proliferation of the Human umbilical cord perivascular (HUCPV) on the surface of the Mg-10Dy-1.5Zn and Mg-15Dy-1.5Zn alloy indicated their good biocompatibility.