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Gastrointestinal (GI) cancers are a leading cause of cancer-related death worldwide, while drug resistance and treatment-related toxicity continue to limit therapeutic efficacy. A growing body of evidence indicates that the gut microbiota-immune axis (GMIA) is closely involved in the development, progression, and treatment response of GI malignancies. In this review, we summarize current understanding of how gut microbial dysbiosis and GMIA dysfunction contribute to GI cancer development and progression. We highlight the role of natural polysaccharides in modulating gut microbial composition and microbial metabolites, thereby influencing host immune responses and exerting antitumor potential in preclinical settings. In addition, we review recent advances in representative natural polysaccharides as promising candidates for the prevention and treatment of gastrointestinal cancers, with an emphasis on their translational prospects and priorities for future investigation.