CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, many studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. In contrast, we demonstrate that absence of iNKT cells dramatically decreased the number of intestinal polyps in APC^Min/+ mice, a model for colorectal cancer. In this model, regulatory iNKT cells promoted intestinal polyp formation by locally enhancing Treg cells and anti-inflammatory M2 macrophages, and immunosuppression of anti-tumor TH1-immunity. Polyp iNKT cells were enriched for IL-10 and IL-17 producing cells, showed a distinct phenotype, and they were negative for the NKT cell transcription factor PLZF. To investigate whether iNKT cell directed therapy could subvert the tumor promoting function of iNKT cells and reduce tumor growth, we performed preclinical therapeutic studies using different iNKT cell ligands. iNKT cell directed immunotherapy could reduce the number and size of polyps, however, the choice of activating ligand, and timing of treatment, was essential.