Tartary buckwheat (Fagopyrum tataricum) is a well-known pseudocereal for its health and economic value. However, abundant antinutritional factors (ANFs) reduces its health benefits. As reported, germination can improve the nutritional profile of grains. In this study, we systematically evaluate the safety of Tartary buckwheat seeds (TB) and Tartary buckwheat sprouts (TBS) used as high active ingredients. After evaluating nutrition levels, bioactive compounds and ANFs in TBS during germinating, 5th-day TBS were selected as the raw material. C57BL/6J mice were gavaged daily with distilled water, TB, or TBS for 6 weeks. The physiological indices related to ANFs were determined. Results showed that the TB intake tends to generate negative effects on the gut microbiota, and organs. Additionally, upon TB intake, the Fe3+ content in serum, trypsin activity in pancreas and jejunum decreased, while the cytokine, IgE, and histamine levels in serum, water content in faeces, cytokine levels in liver and jejunum increased. Conversely, TBS did not induce any obvious negative effects on the above relevant indices and showed better lipid-lowering effect. Altogether, TBS are safer and more effective as a raw material to produce the functional food for long-term consumption with the intention of preventing and treating hyperlipidaemia.