Graphene has been thought to be an ideal reinforcement material for metal matrix composite due to its superior mechanical properties and unique two-dimensional geometry. However, the deformation mechanism of graphene/aluminum matrix composite is still unclear. In this paper, molecular dynamics simulation is used to elucidate the evolution details of the dislocation microstructure and the underlying interaction behavior between dislocation and graphene during nanoindentation of the graphene/aluminum matrix composite with various graphene orientations. To this end, four different cases, i.e. the pure aluminum and the graphene/aluminum matrix composite with the graphene orientation of 90°, 45° and 0° are examined, respectively. Based on the force-indentation depth curve, the interaction behavior between dislocation and graphene and its effect on the plastic zone are analyzed. The results indicate that the graphene can act as an effective dislocation motion barrier, and the elastic deformation of graphene can occur locally along the direction of dislocation slip. Using the visualization technique of dislocation extraction algorithm, the nucleation and propagation of dislocation are investigated. The results show that the differences in interaction behavior between dislocation and graphene with various orientations affect the spreading trend of the plastic zone and the blocking strength of graphene to dislocation. For the composite with the graphene orientations of 45° and 0°, the interaction between graphene and dislocation causes the number of dislocations to increase. Additionally, the plastic zone of the composite with the graphene orientation of 45° is tangent to two symmetrical graphene sheets. For the composite with the graphene orientation of 90°, the interaction between graphene and dislocation shortens the total length of the dislocation line, and the volume shrinkage of plastic zone is most significant after indenter retraction. Here, the hardness is also calculated to quantitatively evaluate the influence of graphene orientation on the mechanical properties of graphene/aluminum matrix composite. The hardness of the composite with the graphene orientation of 45° is highest, which is due to the decrease of the volume of the plastic zone and the increase of dislocation number. The decrease of the hardness of the composite with the graphene orientation of 90° is attributed to the reduction of dislocation number in the plastic zone. However, for the composite with the graphene orientation of 0°, the interaction between graphene and dislocation results in the softening effect, because of a wide range of elastic deformation in the graphene plane. The study can provide a certain theoretical guidance for designing and preparing the high-performance graphene/metal matrix composites.