Gastrointestinal cancer refers to malignancy of the accessory organs of digestion, and it includes colorectal cancer (CRC) and pancreatic cancer (PC). Worldwide, CRC is the second most common cancer among women and the third most common among men. PC has a poor prognosis and high mortality, with 5-year relative survival of approximately 11.5%. Conventional chemotherapy treatments for these cancers are limited due to severe side effects and the development of drug resistance. Therefore, there is an urgent need to develop new and safe drugs for effective treatment of PC and CRC. Historically, natural sources—plants in particular—have played a dominant role in traditional medicine used to treat a wide spectrum of diseases. In recent decades, marine natural products (MNPs) have shown great potential as drugs, but drug leads for treating various types of cancer, including CRC and PC, are scarce. To date, marine-based drugs have been used against leukemia, metastatic breast cancer, soft tissue sarcoma, and ovarian cancer. In this review, we summarized existing studies describing MNPs that were found to have an effect on CRC and PC, and we discussed the potential mechanisms of action of MNPs as well as future prospects for their use in treating these cancers.