We have examined the effects of natural polysaccharides isolated from Phellinus gilvus (PG) in vitro and in vivo against gastric cancer. PG decreased cell proliferation and increased cell apoptosis in a dose-dependent manner in vitro. PG also led to a marked inhibition of tumor growth and significant decrease in the incidence of peritoneal carcinomatosis. Histological analysis of tumor confirmed dramatic increase in tumor cell apoptosis by PG, indicating reduced tumor cell proliferation. These data showed that polysaccharides isolated from PG significantly inhibited tumor growth and metastasis in an orthotopic model of human gastric adenocarcinoma, without detectable problematic adverse effects.