Platelets critically contribute to cancer metastasis by promoting angiogenesis, epithelial–mesenchymal transition, extracellular matrix remodeling, and immune evasion. This study examined the effect of LS extract (LSE), a traditional herbal medicine for activating blood circulation and removing stasis, on platelet activation–driven migration and invasion of colorectal cancer (CRC) cells. LSE markedly suppressed MC38 cell-induced platelet activation and aggregation, as evidenced by reduced ATP release and decreased adhesion to tumor cells. Platelet co-culture significantly enhanced migration and invasion of MC38 cells, confirming the role of platelet activation in CRC metastasis, but these effects were dose-dependently attenuated by LSE. Moreover, elevated transforming growth factor (TGF)-β release in conditioned medium (CM) from MC38–platelet co-culture compared with MC38 mono-culture CM was reduced by LSE. Consistently, phosphorylation of SMAD2/3, a central mediator of TGF-β signaling, was increased by co-culture and significantly inhibited by LSE. Collectively, these findings indicate that LSE suppresses platelet activation and thereby attenuates platelet-driven metastatic behavior of CRC cells through modulation of TGF-β signaling. This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2025-02215233).