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In the gastric mucosa, chronic inflammation due to <i>Helicobacter pylori</i> infection promotes gastrocarcinogenesis. Polysaccharides of <i>Caulerpa lentillifera</i> are well-characterized by broad antimicrobial activity and anti-inflammatory potentials. The present study was undertaken to investigate whether the low molecular sulfate polysaccharides of <i>C. lentillifera</i> (CLCP) exhibit any anti-adhesive activity against <i>H. pylori</i>. After a hot water extraction and purification process, two purified polysaccharide fractions (CLCP-1 and CLCP2) were studied based on structural characterization and bioactivity determination. The results implied that except for the molar ratio, CLCP-1 and CLCP-2 contain high sulfate, mannose, galactose, xylose, glucose levels, and low protein levels. The molecular weight and Fourier transform infrared spectroscopy (FT-IR) assays confirmed that CLCP-1 and CLCP-2 are sulfate polysaccharides with an average molecular weight (Mw) of 963.15 and 648.42 kDa, respectively. In addition, CLCP-1 and CLCP-2 exhibited stronger antibacterial activity against H. pylori. CLCP-1 and CLCP-2 could significantly promote macrophage proliferation and decrease the production of nitric oxide (NO) through downregulated expression of inducible nitric oxide synthase (iNOS). Meanwhile, CLCP-1 and CLCP-2 in this study showed efficiently protected gastric adenocarcinoma (AGS) cells against <i>H. pylori</i> with the inhibition of the IL-8/NF-κB axis. These findings suggested the effect of <i>Caulerpa lentillifera</i> polysaccharides on <i>H. pylori</i> adhesion, a potential supply of nutrients for eradication therapy through the reduction of cell count and inflammation.