Crocetin (CRT), an active compound isolated from saffron, exhibits several pharmacological activities, including anti-tumor and immune-regulatory activities, and is effective against myocardial ischemia and coronary heart disease; however, its low stability and solubility limit its clinical application. Therefore, we investigated CRT inclusion complexes (ICs) with three cyclodextrins-α-CD, HP-β-CD, and γ-CD-suitable for oral administration prepared using an ultrasonic method. Fourier transform infrared spectroscopy and powder X-ray diffraction indicated that the crystalline state of CRT in ICs disappeared, and intermolecular interactions were observed between CRT and CDs. 1H nuclear magnetic resonance and phase solubility studies confirmed CRT encapsulation in the CD cavity and the formation of ICs. In addition, we observed the morphology of ICs using scanning electron microscopy. All ICs showed a high drug encapsulation efficiency (approximately 90%) with 6500-10,000 times better solubilities than those of the pure drug. CRT showed rapid dissolution, whereas pure CRT was water-insoluble. The formation of ICs significantly improved the storage stability of CRT under heat, light, and moisture conditions. Further, the peak time of CRT in rats significantly decreased, and the relative bioavailability increased by approximately 3-4 times. In addition, the oral bioavailability of CRT IC was evaluated. Notably, the absorption rate and degree of the drug in rats were improved. This study illustrated the potential applications of CRT/CD ICs in the food, healthcare, and pharmaceutical industries, owing to their favorable dissolution, solubility, stability, and oral bioavailability.