The study aimed to investigate the antitumor effects of Trapa acornis husks (TAH) extract on SK-BR-3 cells of Her2-positive breast cancer. The bioactive compounds of TAH extracts were analyzed qualitatively and quantitatively by Ultra-Performance Liquid Chromatography/Mass Spectrometry (UPLC-MS)/high-performance liquid chromatographic system (HPLC). The effects of TAH extracts on cell proliferation, cell cycle, and apoptosis of SK-BR-3 cells were determined by CCK-8 and flow cytometry. Besides, the In Vivo antitumor effect of TAH extracts was detected. UPLC-MS/HPLC showed that the main bioactive compounds of TAH were gallic acid and galloylglucose derivatives. TAH extracts significantly inhibited the proliferation of SK-BR-3 cells in a dose- and time-dependent manner (P < 0.01). With the increase of TAH extracts concentration, cells in G2/M stage were increased and cell apoptosis was significantly increased. Immunohistochemical analysis showed that TAH extracts can significantly reduce the positive expression rate of Ki67 and Factor VIII index in tumor tissues. The mRNA expression levels of VEGF, MMP2, MMP9, and uPA were reduced after TAH extracts intervention (P < 0.01). TAH extracts also decreased the protein expression of p-Her2, p-ERK1/2, VEGF, MMP2, MMP9, and uPA (P < 0.01). In conclusion, polyphenol-enriched extracts from TAH might inhibit breast cancer cell proliferation and In Vivo tumor angiogenesis.