With the rapid development of the third-generation semiconductor materials, the chemical mechanical polishing rate and surface quality of single-crystal gallium nitride (GaN) substrates have been a research hot-spot. In this work, the synergistic effect of abrasive friction and glycine (Gly) on improving the chemical mechanical polishing (CMP) performance of single-crystal GaN substrate is proposed and studied systematically. The results indicated that the polishing solutions with Gly have a 2.3-fold improvement in material removal rate (MRR) as well as scratch-free surface than that without Gly. The maximum MRR of the single-crystal GaN substrate is 129.4 nm/h with surface roughness (Ra) of 0.64 nm attained by using the polishing solutions containing only 3 wt% potassium persulfate (K2S2O8). In contrast, when Gly is added as a reaction reagent, which can be activated by abrasive friction, the maximum MRR is increased to 304.2 nm/h with Ra of 0.42 nm. Meanwhile, the epitaxial evaluation indicates that two-dimensional (2D) MoS2 grown on processed single-crystal GaN substrate has superior crystalline quality and optical properties. Finally, the polishing mechanism of the single-crystal GaN substrate using the mixed solutions of K2S2O8 and Gly is discussed. The proposed CMP method has potential applications in the semiconductor and microelectronics industries.