This study assessed the effects of thermal (40, 60, 80, 100 and 127 °C) and high hydrostatic pressure (HHP, 200, 400 and 600 MPa) treatments on the in vitro digestibility and structural properties of sweet potato protein (SPP). The results showed that the in vitro digestibility of SPP increased significantly with increasing heating temperature and heating time (0-60 min), while HHP treatment had little or no effect. Native SPP denaturation temperature (T d ) and enthalpy change (ΔH) were 89.0 °C and 9.6 J/g, respectively. Thermal and HHP treated SPP had T d of 84.6-88.9 °C and 86.4-87.6 °C, respectively. ΔH of thermal treated SPP was 3.6-6.4 J/g, while that of HHP treated SPP was 5.9-7.8 J/g. The differential scanning calorimetry (DSC) results demonstrated that HHP and thermal treatments both significantly reduced SPP thermodynamic stability. Circular dichroism analyses revealed that native SPP contains α-helixes, β-sheets and random coils (4.3, 48.0 and 47.7%, respectively). After thermal treatment at 127 °C for 20 min, the content of α-helixes and turns increased significantly (13.2 and 27.6%, respectively), whereas the content of β-sheets decreased significantly (12.3%). In contrast, HHP treatment increased the content of β-sheets, but decreased the content of random coils. This study suggested that the SPP structure changes might be the main reason affecting the in vitro digestibility of SPP, and thermal treatment was more effective at changing SPP secondary structures and improving in vitro SPP digestibility than HHP treatment.