Abstract: Objective: To investigate the effects of dietary supplementation with tartary buckwheat-derived nanoparticles (TBDNs) on key physiological parameters in mice. Methods: Twenty-four C57BL/6 mice were randomly assigned to two groups: a normal control group and a TBDNs group. Changes in body weight, blood biochemical markers, cell histology and immunohistochemistry of the colon and liver, as well as intestinal flora composition, were analyzed. Results: Compared to the normal diet group, the 10 mg TBDNs group exhibited significant reductions in body weight, triglyceride levels, uric acid levels, and alanine aminotransferase activity (P<0.01). Physiological indicators such as aspartate aminotransferase, cholesterol, high-density lipoprotein, low-density lipoprotein, and creatinine, as well as liver and colon tissues, showed no significant changes (P>0.05). The abundance of intestinal Lactobacillus, Turicibacter, and Lachnoclostridium species were all significant increased (P<0.05). Conclusion: Intake of TBDNs has discernible physiological effects on mice, however, further investigations are required to elucidate its underlying mechanisms and potential health benefits. These findings provide novel insights and data for nutritional evaluation of tartary buckwheat.