The therapeutic potential of Sargassum siliquosum grown in Australian tropical waters was tested in a rat model of metabolic syndrome. Forty-eight male Wistar rats were divided into four groups of 12 rats and each group was fed a different diet for 16 weeks: corn starch diet (C); high-carbohydrate, high-fat diet (H) containing fructose, sucrose, saturated and trans fats; and C or H diets with 5% S. siliquosum mixed into the food from weeks 9 to 16 (CS and HS). Obesity, hypertension, dyslipidaemia, impaired glucose tolerance, fatty liver and left ventricular fibrosis developed in H rats. In HS rats, S. siliquosum decreased body weight (H, 547 ± 14; HS, 490 ± 16 g), fat mass (H, 248 ± 27; HS, 193 ± 19 g), abdominal fat deposition and liver fat vacuole size but did not reverse cardiovascular and liver effects. H rats showed marked changes in gut microbiota compared to C rats, while S. siliquosum supplementation increased gut microbiota belonging to the family Muribaculaceae. This selective increase in gut microbiota likely complements the prebiotic actions of the alginates. Thus, S. siliquosum may be a useful dietary additive to decrease abdominal and liver fat deposition.