High- and medium-entropy alloys have attracted considerable attention because of their innovative design concepts. The VCoNi medium-entropy alloy with equiatomic ratio, a distinctive type of medium-entropy alloy, is characterized by a fcc structure. As it exhibits remarkable mechanical properties such as strength and plasticity across a broad temperature spectrum, it is suitable for versatile applications. Current research on VCoNi medium-entropy alloys predominantly focuses on the alloy design and the manipulation of heat treatment technologies to enhance mechanical properties with relatively less emphasis on elucidating plastic deformation mechanisms. A profound understanding of these mechanisms is imperative for controlling their properties. Although previous studies have revealed plastic deformation mechanisms mediated by dislocations in VCoNi medium-entropy alloys, the impact of grain orientation on dislocation movement and interaction mechanisms remains elusive. Nanoindentation technology has been widely used to assess plastic deformation behavior and dislocation evolution in materials. Grain orientation profoundly influences the mechanical properties and plastic deformation behavior of materials at the microscale. Therefore, investigating the influence of grain orientation on the plastic deformation mechanism in the VCoNi medium-entropy alloy is of great importance. A comprehensive understanding of plastic deformation and dislocation interactions can be achieved by analyzing slip steps generated by nanoindentation. This study delves into the plastic deformation behavior of VCoNi medium-entropy alloy in {101}, {111}, and {001} grains using nanoindentation. By analyzing the evolution of slip steps and load-displacement curves, it concentrates on the influence of crystal orientation on plastic deformation behavior and explores the intricate relationship among dislocation interactions, load-displacement behavior, and dislocation motion. The grain orientation in the VCoNi medium-entropy alloy dictates the activation and sequence of slip systems induced by nanoindentation, thereby substantially influencing the morphology of indentations, surrounding slip steps, and load-displacement behavior. The slip steps on the same slip plane in each grain preferentially appear on a positively inclined slip plane. On {101} grains, the slip steps appear on the (111) and (\mathrm{11}\overline{\mathrm{1}}) slip planes initially, and then on the (\mathrm{1}\overline{\mathrm{1}}\overline{\mathrm{1}}) and (\mathrm{1}\overline{\mathrm{1}}\mathrm{1}) slip planes. In {111} grains, the slip steps appear on the (\mathrm{11}\overline{\mathrm{1}}), (\mathrm{1}\overline{\mathrm{1}}\overline{\mathrm{1}}), and (\mathrm{1}\overline{\mathrm{1}}\mathrm{1}) slip planes. On {001} grains, the slip steps appear on the four {111} slip planes. {101}, {111}, and {001} grains exhibit butterfly-shaped, nested triangle-shaped, and cross-shaped overall indentation morphologies, respectively. Additionally, only a limited occurrence of double cross-slip is observed at the edges of the slip steps in {101} and {001} grains. The analysis of dislocation interactions revealed that on {101} grains, dislocation reactions tended to form Lomer-Cottrell locks and Glissile junctions, in {111} grains they tended to form Collinear junctions and Lomer-Cottrell locks, and in {001} grains they tended to form Glissile junctions. This determination influences the subsequent pop-in behavior in the load-displacement curves of different grains.