Zika virus (ZIKV) is an arthropod-borne flavivirus that reemerged in 2007 and, since then, has caused several outbreaks and spread to over 80 countries worldwide. Along with this, ZIKV infections have been associated with severe clinical outcomes, including neurological manifestations, especially in newborns, posing a major threat to human health. However, there are no licensed vaccines or specific antiviral agents available yet; thereby, there is an urgent need for the discovery of novel therapeutic strategies to fight this infection. In this context, seaweeds are proven sources of biologically relevant products, including antiviral ones, that remain poorly explored. Herein, we evaluated the antiviral potential of the dichloromethane extract of the red seaweed Bryotamnion triquetrum against ZIKV. MTT assay was carried out to evaluate the extract's toxicity in Vero cells, while standard plaque assays were performed for viral titer quantification in the antiviral assays. The B. triquetrum extract possessed great inhibitory activity on the ZIKV replication in Vero cells, with an EC50 of 1.38 µg/ml and a higher selectivity index than ribavirin (289.85 and 75.20, respectively), a licensed antiviral drug. The investigation of its mechanism of action revealed a moderate virucidal effect while it strongly impaired virus replication at both early and late steps of the virus replication cycle with moderate inhibition at the attachment stage. Finally, the B. triquetrum extract presented a remarkable synergistic effect with ribavirin at suboptimal concentrations, which also highlights the promising antiviral potential of this product as a drug candidate to combat ZIKV infection. Keywords: Rhodophyta; Algae; arbovirus; antiviral; Zika.