Sulindac is a well-known anti-inflammatory agent, sometimes employed as an adjuvant in antitumor therapy. Due to the recent interest in sulfoximine for its potential chemotherapeutics, we decided to transform sulindac and its methyl ester into the corresponding sulfoximines to test their antitumor activity. These compounds were fully characterized. Eventually, sulindac, sulindac methyl ester and the two novel corresponding sulfoximines were tested against malignant cells of U-87 glioblastoma, MCF-7 human breast cancer, HepG2 human liver hepatocellular carcinoma, CaCo-2 human colon cancer, and HeLa human cervical cancer. Interesting preliminary results were observed that encourage new investigations in this research theme.