Maggots contain various kinds of polysaccharides and recent studies mostly concentrated on their anti-inflammatory functions. While the molecule mechanisms related to the polysaccharides inhibiting carcinogenesis remains unclear. Here we characterized the polysaccharides extracted from maggot (MEs) determining their anti-colon cancer potentials. ME in this study were composed of glucose, mannose, galactose, arabinose and xylose. ME dose-and time-dependently inhibited viability and obviously induced G0/G1 phase arrest in human colon cancer cells. Additionally, Proteomics and western blotting proved that ME suppressed the expression of GPX4 and increased the expression of HMOX1 in vivo and vitro. ME promoted ferroptosis in HCT116 and LOVO cells, reversing ROS, lipid peroxidation and GSSG/GSH radio level. In general, the findings stated that the polysaccharides provided effects of inducing colon cancer ferroptosis, uncovering potential function of ME from maggot as a candidate compound.