Natural remedies have been indispensable to traditional medicine practices for generations, offering therapeutic solutions for various ailments. In modern times, these natural products continue to play a pivotal role in the discovery of new drugs, especially for cancer treatment. The marine ecosystem offers a wide range of plants with potential anticancer activities due to their distinct biochemical diversity and adaptation to extreme situations. The seagrass Halodule uninervis is rich in diverse bioactive metabolites that bestow the plant with various pharmacological properties. However, its anticancer activity against invasive triple-negative breast cancer (TNBC) is still poorly investigated. In the present study, the phytochemical composition of an ethanolic extract of H. uninervis (HUE) was screened, and its antioxidant potential was evaluated. Moreover, the anticancer potential of HUE against MDA-MB-231 cells was investigated along with the possible underlying mechanisms of action. Our results showed that HUE is rich in diverse phytochemicals that are known for their antioxidant and anticancer effects. In MDA-MB-231 cells, HUE targeted the hallmarks of cancer, including cell proliferation, adhesion, migration, invasion, and angiogenesis. The HUEmediated anti-proliferative and anti-metastatic effects were associated with the downregulation of the proto-oncogenic STAT3 signaling pathway. Taken together, H. uninervis could serve as a valuable source for developing novel drugs targeting TNBC.