Effect of high pressure processing (HPP) on buckwheat nutritional properties is investigated in this study. The results indicated that the digestion of buckwheat starches of untreated and HPP treated at room temperature (RT) showed an “internal corrosion” pattern. However, an “exocorrosion” digestion behavior was observed for the starches of HPP treated sample at 45 °C, which might be due to the formation of amylose–lipid complexes during the process as revealed by X-ray diffraction (XRD). HPP treatment at 45 °C increased the antioxidant activity of the buckwheat as measured using 1,1′-diphenyl-2-picrylhydrazylvalue (DPPH) and iron chelating capacity (ICC) compared to untreated sample (P < 0.05), which might be associated with the release of bound phenolic compounds. More importantly, this is the first study to investigate the ability of buckwheat extract for inhibiting the formation of fat droplets using a C3H10T1/2 mesenchymal stem cell line, and found that the extract of buckwheat after HPP treatment at 45 °C demonstrated significant anti-adipogenic effects. This study suggested the HPP treatment at an increased temperature (45 °C) achieved a better nutritional value of the buckwheat than both untreated and treated at RT.