The processing of tomato fruit into puree, juices, ketchup, sauces, and dried powders generates a significant amount of waste in the form of tomato pomace, which includes seeds and skin. Tomato processing by-products, particularly seeds, are reservoirs of health-promoting macromolecules, such as proteins (bioactive peptides), carotenoids (lycopene), polysaccharides (pectin), phytochemicals (flavonoids), and vitamins (α-tocopherol). Health-promoting properties make these bioactive components suitable candidates for the development of novel food and nutraceutical products. This review comprehensively demonstrates the bioactive compounds of tomato seeds along with diverse biomedical activities of tomato seed extract (TSE) for treating cardiovascular ailments, neurological disorders, and act as antioxidant, anticancer, and antimicrobial agent. Utilization of bioactive components can improve the economic feasibility of the tomato processing industry and may help to reduce the environmental pollution generated by tomato by-products.