A versatile and popular Cucurbitaceous vegetable, pumpkin has recently gained much attention because of its variety of phytochemicals and health advantages. Pumpkins are a type of winter squash, traditionally with large, spherical, orange fruits and a highly nutrient food. Pumpkin by-products comprise various parts, such as seeds, peels, and pulp residues, with their bioactive composition and many potential benefits poorly explored by the food industry. Pumpkin and their by-products contain a wide range of phytochemicals, including carotenoids, polyphenols, tocopherols, vitamins, minerals, and dietary fibers. These compounds in pumpkin by-products exhibit antioxidant, anticancer, anti-inflammatory, anti-diabetic, and antimicrobial properties and could reduce the risk of chronic diseases. This comprehensive review aims to provide a detailed overview of the phytochemicals found in pumpkin and its by-products, along with their extraction methods, health benefits, and diverse food and industrial applications. This information can offer valuable insights for food scientists seeking to reevaluate pumpkin’s potential as a functional ingredient. Reusing these by-products would support integrating a circular economy approach by boosting the market presence of valuable and sustainable products that improve health while lowering food waste.