In recent years, dietary products with quinoa and buckwheat have attracted attention mostly due to the high nutritive value of their protein fraction. However, their dietary effect on intestinal microbiota activity and related systemic responses are still poorly understood. Therefore, a 2 week study of twenty-eight growing male Wistar rats was conducted to investigate the effects of quinoa (QU) and buckwheat (BK) protein-rich flours on the growth parameters, intestinal microbial activity, plasma lipid profile, and inflammatory markers. The biological value of protein and body weight gain were considerably increased in the QU and BK groups compared with those in the soy protein isolate group. Moreover, both flours increased the microbial activity of α-glucosidase, β-glucosidase, and α-galactosidase and the concentration of short-chain fatty acids in the caecum. The studied flours favourably reduced the plasma total cholesterol and LDL cholesterol. In rats fed a diet with QU, elevated levels of plasma interleukin 6 and alanine transaminase were observed. The effect of QU on inflammatory markers may be related to the increased expression of aryl hydrocarbon receptor in the liver and to the decreased level of plasma albumin. In conclusion, quinoa and buckwheat protein-rich flours are valuable sources of proteins that favourably affect growth parameters, gut metabolism, and blood lipid profile in rats; however, only the buckwheat flour has no effect on inflammatory processes.