We use molecular dynamics to assess the effect of grain boundaries and rigid intergranular inclusions on plastic deformation in nickel (Ni) containing helium (He) bubbles and self-interstitial atom clusters. Our simulations show that plasticity in Ni bicrystals is relatively uniform, with no localized slip bands or nano-twins. We attribute this behavior to grain boundaries, which block dislocations and favor activation of new sources over persistent slip along a single plane. While there is no initiation of intergranular cracks, He bubbles at matrix/inclusion interfaces elongate along the tensile axis and migrate towards regions of high tension, potentially setting the conditions for formation of crack-like flaws via bubble coalescence. We discuss the implications of our work for understanding degradation of mechanical properties in Ni-base alloys in nuclear reactors.