<p>The complex interplay between parasites and cancer is yielding promising advances in the field of cancer therapeutics. This study explored the in vitro anti-cancer potential of parasite immunomodulators (antigens and antibodies) of <i>Schistosoma mansoni</i>,<i> Trichinella spiralis</i>, and <i>Toxoplasma gondii</i> on human HT-29 colorectal and HepG2 hepatocellular carcinoma cells using the MTT assay. Results revealed that those parasites’ immunomodulators exhibited antineoplastic activity and demonstrated a statistically significant inhibition of both cancer cell lines’ proliferation (P ˂0.05). Notably, <i>Trichinella spiralis</i> antigens and antibodies and anti-<i>Toxoplasma gondii</i> antibodies demonstrated the most statistically significant inhibitory effects on HT-29 colorectal cancer cells (36.65%, 49.9% and 50.43% respectively). For HepG2 hepatocellular carcinoma cells, <i>Trichinella spiralis</i> antigens and antibodies, as well as <i>Toxoplasma gondii</i> antigen, displayed the most statistically significant inhibitory effects (38.27%, 48.25% and 34.68% respectively). Interestingly, parasitic antibodies are particularly noteworthy, exhibiting the most significant inhibitory effects on both cancer cell lines. To the best of our knowledge, this is the first study to demonstrate the antineoplastic activity of parasites’ antibodies against human colorectal cancer and hepatocellular carcinoma. These findings could enlighten the path for promising cancer therapeutic candidates. Future research should explore the antineoplastic potential of a broader range of parasites’ immunomodulators and identify their mechanisms of action. This could represent a qualitative shift towards the development of innovative cancer therapeutic antibodies and cancer vaccine candidates of parasitic origin for cancer-targeted immunotherapy.</p> Graphical Abstract <p></p>