Abstract: Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), ranks among the most prevalent malignancies and is a leading cause of cancer-related mortality worldwide. Therefore, there is an urgent need to identify novel anti-pancreatic cancer agents. This study reports a newly identified homogeneous polysaccharide, designated ESPPW, isolated from Arthrospira platensis (A. platensis). The molecular weight of ESPPW is estimated at 356 kDa, and it consists predominantly of glucose and rhamnose, with minor amounts of mannose, glucuronic acid, galacturonic acid, galactose, xylose, arabinose, and fucose. ESPPW inhibits the proliferation and migration of PDAC cells both in vitro and in vivo. Mechanistic investigations reveal that ESPPW induces apoptosis through activation of caspase-3 and is associated with upregulation of the tumor-suppressor protein p53. Notably, treatment with 2.8 nmol·L⁻¹ of ESPPW leads to significant time-dependent downregulation of galectin-3 (Gal-3) and glypican-6 (GPC-6). These findings are corroborated by immunohistochemical analysis of tumor xenograft tissues. Furthermore, overexpression of Gal-3 and GPC-6 reverses the pro-apoptotic effect of ESPPW, as indicated by restored cycle regulatory proteins (CDK2) expression. In conclusion, these data demonstrate that ESPPW suppresses PDAC cell growth by promoting apoptosis and disrupting the functional activity of Gal-3 and GPC-6.