Circular dichroism (CD) spectroscopy is a powerful method for studying the chirality of biologically active natural products and also for clarifying the mechanisms of their biological activities. In this chapter, the principle and applications of electronic CD (ECD) spectroscopy to natural products are reviewed. The concepts of optical rotation (OR), CD, and ultraviolet (UV) spectroscopy are explained together with definition of parameters, measurement procedures, and some significant equations for calculating optical activity. ECD Cotton effects are classified into several groups depending on the chromophores and mechanisms for which some empirical and nonempirical CD methods have been proposed. Among them the CD exciton chirality method is the most useful for determining the absolute configurations (ACs) of natural products in a nonempirical manner. The principles of the exciton chirality method are explained together with selected chromophores suitable for exciton coupling, para-substituted benzoates, cinnamate, β-naththoate, tetraphenyl-porphyrin-carboxylate, 2,3-naphthalenedicarboximido chromophores, red-shifted chromophores, porphyrin tweezers, etc. Another useful method for determining ACs of natural products is the ab initio molecular orbital (MO) calculation of ECD and OR. Applications of these CD methods to various natural products and their intermolecular interactions are discussed in this chapter.