Zn-Mn alloys are considered promising biodegradable metals for orthopedic applications due to their large elongation and favorable osteogenicity. However, the corrosion rate of Zn-Mn alloys could be improved to meet the degradation requirement for orthopedic implants. In this study, a Zn-1.5Mn alloy was prepared via high-pressure solid-solution (HPSS) treatment at 5 GPa and 380 °C for 1 h to cast ingots. Microstructural evaluation revealed the HPSS treatment caused a phase transition from a ζ-MnZn13 phase to an ε-MnZn3 phase. The electrode potential difference between the ε-MnZn3 and the α-Zn was significantly larger than between the ζ-MnZn13 and the α-Zn, leading to an accelerated corrosion rate of the HPSS-treated alloy. It showed an electrochemical corrosion rate of 0.343 mm/y and an immersion degradation rate of 0.028 mm/y, while the as-cast (AC) Zn-1.5Mn displayed an electrochemical corrosion rate of 0.216 mm/y and an immersion degradation rate of 0.026 mm/y. Further, the HPSS-treated Zn-1.5Mn exhibited a compressive yield strength of 202 MPa and a microhardness of 83.48 HV. In addition, the HPSS-treated Zn-1.5Mn exhibited a cell viability toward human umbilical vein endothelial cells (HUVEC) comparable to its AC and atmospheric pressure solid-solution-treated (APSS-treated) counterparts toward HUVEC, along with improved antibacterial activity.