The human placenta plays a key role in reproduction and serves as a major interface for maternofetal exchange of nutrients. Study of human placenta pathology presents a great experimental challenge because it is not easily accessible. In this paper, a 3D placenta-on-a-chip model is developed by bioengineering techniques to simulate the placental interface between maternal and fetal blood in vitro. In this model, trophoblasts cells and human umbilical vein endothelial cells are cultured on the opposite sides of a porous polycarbonate membrane, which is sandwiched between two microfluidic channels. Glucose diffusion across this barrier is analyzed under shear flow conditions. Meanwhile, a numerical model of the 3D placenta-on-a-chip model is developed. Numerical results of concentration distributions and the convection–diffusion mass transport is compared to the results obtained from the experiments for validation. Finally, effects of flow rate and membrane porosity on glucose diffusion across the placental barrier are studied using the validated numerical model. The placental model developed here provides a potentially helpful tool to study a variety of other processes at the maternal–fetal interface, for example, effects of drugs or infections like malaria on transport of various substances across the placental barrier.