Metastasis, the dissemination of cancer cells, is promoted by metabolic reprogramming and the expression of Caveolin-1 (CAV1). Curcumin and phlorotannins have antioxidant and antitumoral activities. This study compares the potential anti-metastatic effects of phloroglucinol (phlorotannin monomer, PHG) and curcumin-loaded nanoemulsions (CUR-NEM) in CAV1-expressing cells. To that end, the metastatic cancer cell lines (MDA-MB-231 and B16-F10), which either express or not CAV-1, were treated with either PHG or CUR-NEM. The results demonstrate that PHG and CUR-NEM prevent cancer cell migration in vitro and metastasis in vivo of CAV1-expressing cells. Moreover, in the cancer cells treated with PHG or CUR-NEM, a significant reduction in glycolysis due to the inhibition of hexokinase activity was detected. These findings show that both PHG and CUR-NEM prevent metastasis in a preclinical animal model and link this ability to the inhibition of hexokinase 2, highlighting their potential significance as cancer therapeutics. © 2025 Elsevier B.V., All rights reserved.