<p>Carotenoids are natural isoprenoid compounds with diverse health benefits, widely used in food, cosmetics, and pharmaceuticals. However, low bioavailability and chemical instability limit their effect according to their fat-soluble property. Some strategies such as nanoencapsulation, emulsions, complexation, and glycosylation have been explored to enhance carotenoid bioavailability. In addition, there is growing interest in water-soluble carotenoids in nature. This review focuses on recent advancements in improving the water solubility of carotenoids, with special attention to naturally occurring water-soluble carotenoids like crocin. Research progress on the biosynthetic pathways of crocin derived from natural plants is summarized. In addition, heterologous production using genetic and metabolic engineering in plants and microorganisms is discussed, along with its potential applications in bio-industries. Finally, the promising pharmacological properties of crocin, including antioxidant, anti-inflammatory and anticancer effects, are presented. The sustainable production of water-soluble carotenoids through biological synthesis offers a potential for improved absorption and functionality.</p>