Recently, we have proposed that quinoa yoghurt (QY) has the anti-diabetic properties based on an in vitro study. Here, its antidiabetic activity was further validated by investigating its hypoglycemic and hypolipidemic influence in high fat diet/streptozotocin-induced type 2 diabetes mellitus (T2DM) mice. The results showed that QY increased the body weights of and reduced the fasting blood glucose levels in T2DM mice. QY significantly (p < 0.05) reduced the serum levels of total cholesterol, triglyceride and LDL-C, while it increased the HDL-C level. In addition, the hepatic glycogen content, and superoxide dismutase, catalase, and glutathione peroxidase activities were significantly (p < 0.05) increased, while lipid peroxidation was remarkably reduced. Sprouted QY had the highest influence on serum oxidation when compared with non-germinated QY. The level of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) were significantly (p < 0.05) decreased, while the level of anti-inflammatory cytokine IL-10 was increased. Histopathological studies showed that QY protected the tissue structure of the liver of T2DM mice. Immunohistochemistry showed that QY increased AKT-2 and AMPK-α2 expressions, while it suppressed p85. The qRT-PCR analysis indicated that QY exerted its hypoglycemic and anti-hyperlipidemic effects through the AKT/AMPK/PI3K signaling pathway. Germination significantly (p < 0.05) influenced the glucose and lipid homeostasis in T2DM mice in such a way that sprouted QY showed the highest hypoglycemic and cholesterol-lowering effects when compared with non-germinated QY.