- (1) Background: The red seaweed Palmaria mollis (PM), which has a bacon-like taste, is increasingly being included in Western diets. In this study, we evaluate anti-obesity effects of PM using diet-induced obese (DIO) zebrafish and mice models. (2) Methods: We fed PM-containing feed to DIO-zebrafish and mice, and evaluated the anti-obesity effects We also analyzed gene expression changes in their liver and visceral adipose tissues (VAT). (3) Results: PM ameliorated several anti-obesity traits in both animals, including dyslipidaemia, hepatic steatosis, and visceral adiposity. In liver tissues of DIO-zebrafish and mice, PM upregulated gene expressions involved in peroxisome proliferator-activated receptor alpha (PPARA) pathways, and downregulated peroxisome proliferator-activated receptor gamma (PPARG) pathways, suggesting that the lipid-lowering effect of PM might be caused by activation of beta-oxidation and inhibition of lipogenesis. In VAT, PM downregulated genes involved in early and late adipocyte differentiation in zebrafish, but not in mice. (4) Conclusions: We have demonstrated that PM can prevent hepatic steatosis and visceral adiposity for the first time. Dietary supplementation of PM as a functional food may be suitable for obesity prevention and reduction in the prevalence of obesity-related diseases.