Background: Colorectal cancer (CRC) is a global health concern with significant mortality rates. Lifestyle factors and heightened oxidative stress contribute to its development. CRC's genetic instability is driven by CpG island methylator phenotype (CIMP), chromosomal instability (CIN), and microsatellite instability (MSI) pathways, with oxidative stress playing a critical role. It disrupts DNA repair mechanisms, enhancing CRC development. Main Body of the Abstract: Oxidative stress, stemming from reactive species like hydroxyl radicals, peroxynitrite, and superoxide anions, leads to DNA damage, mutagenesis, and genomic instability in CRC. The delicate balance between ROS production and antioxidant defenses tips towards oxidative stress, fostering cancer cell proliferation and DNA oxidation. Oxidative damage results in mutagenesis, carcinogenesis, and aging, with oxidative DNA damage observed as GC base pair changes. Reactive oxygen species (ROS) also play a significant role in CRC initiation, promotion, and progression. The JAK/STAT, PI3K/AKT, and COX pathways, disturbed by oxidative stress, are implicated in CRC pathogenesis. Redox-modifying drugs show promise in targeting CRC cell lines, exploiting their sensitivity to oxidative stress. Short Conclusion: Oxidative stress is pivotal in CRC development and progression, affecting DNA integrity and signaling pathways. Understanding of the intricate interplay between oxidative stress and colon cancer, offers valuable insights for future research and therapeutic strategies. Combining ROS modulators with chemotherapy could enhance CRC treatment outcomes, highlighting the significance of redox biology in CRC as a potential therapeutic target.