<p>Colorectal cancer (CRC) remains a significant global health challenge, with oxidative stress and chronic inflammation being key drivers of its pathogenesis. Non-pharmacological interventions may be crucial in mitigating these processes. This narrative review explores the synergistic potential of Spirulina supplementation and aerobic exercise as a complementary therapeutic strategy for CRC. Spirulina, a nutrient-rich microalga, is recognized for its potent antioxidant and anti-inflammatory properties, primarily attributed to compounds like phycocyanin. It has been shown to modulate critical signaling pathways, such as MAPK/ERK and PI3K/AKT, which are often dysregulated in CRC, thereby inhibiting cancer cell proliferation and inducing apoptosis. Similarly, aerobic exercise has demonstrated profound effects on the tumor microenvironment. Regular physical activity enhances systemic immunity by increasing the activity and infiltration of natural killer (NK) cells, reducing immunosuppressive metabolites like lactate, and promoting a healthy gut microbiota. The combined effect of Spirulina's molecular-level interventions and the systemic benefit of aerobic exercise presents a compelling, dual-pronged approach. By targeting distinct but interconnected pathways, this synergy could more effectively counteract the oxidative stress and inflammatory cascades that fuel colorectal tumorigenesis. This review consolidates the current understanding of these individual interventions and highlights the promising, yet under-explored, potential of their combined application in CRC management. Further clinical investigation into this synergistic strategy is warranted to assess efficacy and establish evidence-based guidelines for its use in integrative oncology.</p>