Carotenoids are a large and diverse group of compounds that have been shown to have a wide range of potential health benefits. While some carotenoids have been extensively studied, many others have not received as much attention. Studying the physicochemical properties of carotenoids using electron paramagnetic resonance (EPR) and density functional theory (DFT) helped us understand their chemical structure and how they interact with other molecules in different environments. Ultimately, this can provide insights into their potential biological activity and how they might be used to promote health. In particular, some rare carotenoids, such as sioxanthin, siphonaxanthin and crocin, that are described here contain more functional groups than the conventional carotenoids, or have similar groups but with some situated outside of the rings, such as sapronaxanthin, myxol, deinoxanthin and sarcinaxanthin. By careful design or self-assembly, these rare carotenoids can form multiple H-bonds and coordination bonds in host molecules. The stability, oxidation potentials and antioxidant activity of the carotenoids can be improved in host molecules, and the photo-oxidation efficiency of the carotenoids can also be controlled. The photostability of the carotenoids can be increased if the carotenoids are embedded in a nonpolar environment when no bonds are formed. In addition, the application of nanosized supramolecular systems for carotenoid delivery can improve the stability and biological activity of rare carotenoids.