Tomatoes (Solanum lycopersicum) are of great significance in terms of the worldwide consumption of nutritional diets. More than half of the production is sold as fresh products, while the whole fruit is still typically processed into various products, including canned tomatoes, paste, juice, and puree. Tomatoes are rich in phenolic compounds, which are generally present as soluble and bound forms in nature. Large amounts of nutritional and bioactive compounds such as phenolics, flavonoids, carotenoids, vitamins, minerals and glycoalkaloids have drawn increasing interest in tomato fruits. However, there appears to be a certain anti-nutritional compound that negatively influences human health. As the role of antioxidants in human nutrition has gained increased interest, the bioavailability of tomato fruits is of great importance to be researched and studied, especially due to their associated health benefits for a number of chronic diseases, including certain types of cancer and cardiovascular disease. Nevertheless, the processing of tomatoes into various end products, including mechanical and heat treatments, is considered to be one of the most significant factors that are potentially affected by those nutritional properties, anti-nutritional compounds and causing changes in the bioavailability of antioxidants. In this review, the nutritional and anti-nutritional compounds, and related health and side effects were discussed. The review also focused on the effects of different food processing techniques on the in vivo and in vitro bioavailability of tomato antioxidants.