Similar to conventional engineering fabrication processes, tribological performance of drugs and pills in pharmaceutical manufacturing plays an important role in quality and product yields. In the present research, we investigate the effects of crystal structures of workpiece materials on their tribological performance in conditions typical of pharmaceutical manufacturing processes. Sorbitol composites containing gold nanoparticles were evaluated for material properties and tribological performance. It was found that the control exhibited nonordered gamma forms of sorbitol, while the samples containing rod nanoparticles showed a collection of tiny needlelike crystals of gamma phase. Spherical nanoparticles precipitated beta and alpha phases of sorbitol, which were not seen in the other samples. These variations in the crystal structure resulted in an unusual wear behavior, leading to high friction and softness in the case of the nanocomposites. The nanoparticles were found to influence the crystal structure of the sorbitol matrix, resulting in mechanical and tribological behaviors.