Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that inhibits COX-1 and COX-2. Sulindac exhibits anti-inflammatory, neuroprotective, anti-metastatic, and anticancer chemotherapeutic activities. In vitro, sulindac inhibits phosphodiesterases (PDEs), increasing levels of cGMP and activation of PKG and inhibiting expression of β-catenin. In animal models of ischemic stroke, sulindac decreases infarct size and increases expression of Akt, Bcl-2, and HSP 27. This compound inhibits invasion of breast cancer cells and colon cancer cells by decreasing NF-κB-mediated transcription of several miRNAs. Additionally, sulindac downregulates expression of STAT3 and survivin and decreases cell proliferation and tumor growth in cellular and animal models of laryngeal cancer.