Purpose Metabolic syndrome is characterized by hyperglycemia, hyperlipemia and exacerbated oxidative stress. The aim of the study was to determine whether Spirulysat(R), a Spirulina liquid extract (SLE) enriched in phycocyanin, would prevent metabolic abnormalities induced by high-fat diet. Methods The effect of acute SLE supplementation on postprandial lipemia and on triton-induced hyperlipidemia was studied in hamster fed control diet (C). The effect of chronic SLE supplementation on lipid content in plasma, liver and aorta, and on glycemia and oxidative stress was studied in hamster fed control (C) or high-fat diet (HF) for two weeks and then treated with SLE for two weeks (CSp and HFSp) or not (C and HF). Results The acute SLE supplementation lowered plasma cholesterol and non-esterified fatty acid concentrations after olive oil gavage (P < 0.05) in CSp, while no effect was observed on triglyceridemia. HFD increased plasma MDA, basal glycemia, triglyceridemia, total plasma cholesterol, VLDL, LDL and HDL cholesterol, ceramide, sphingomyelin and glucosylceramide content in liver in HF compared to C (P < 0.05). SLE did not affect SOD and GPx activities nor total antioxidant status in HFSp group but lowered glycemia, glucoceramide and cholesterol in liver and cholesterol in aorta compared to HF (P < 0.05). SLE also decreased HMGCoA and TGF-beta 1 gene expression in liver (P < 0.05) and tended to lower G6Pase (P = 0.068) gene expression in HFSp compared to HF. Conclusion Although 2-week SLE supplementation did not affect oxidative stress, it protected from hyperglycemia and lipid accumulation in liver and aorta suggesting a protective effect against metabolic syndrome.