Strain-relieved GaSb quantum dots on GaAs can be achieved by either periodic interfacial misfit (IMF) or the conventional Stranski–Krastanov (SK) growth modes by changing the growth parameters. In this study, the Sb interfacial treatment was employed to improve the GaSb crystal quality including low defect density, smooth surface morphology, and high hole mobility. This technique yields two-dimensional (2D) islands with a height as low as 1.7 nm and width up to 190 nm in the IMF growth mode. In contrast to the interfacial treatments conventionally employed in the initial strain relaxation of GaSb/GaAs hererostructure, the Sb treatment promotes the formation of strong Ga-Sb bonds on the surface of the grown island, which effectively reduces the interfacial free energy and thus promotes the formation of 2D islands. With the Sb interfacial treatment, a high-relaxation 100-nm GaSb epilayer was grown on the GaAs substrate, the epilayers was strain relaxed and exhibited enhanced electrical properties with a high hole mobility of ~667 cm2 V−1 s−1 and with superior optical properties as evidenced by the photoluminescence B-line peak. The results of this study demonstrate an effective interfacial-treatment growth technique to relax the initial strain for the highly mismatched GaSb layers grown on a GaAs substrate.