Introduction: Cannabidiol (CBD) has several potential benefits and therapeutic uses, especially in pain, inflammation, and anxiety. CBD has high hydrophobicity and very low solubility in water. CBD has also shown exceptionally low oral-gastrointestinal (oral-GI) bioavailability. In this study, we aimed to examine the oral gastrointestinal absorption and subsequent bioavailability of CBD in a nanoemulsion formulation prepared by Pressure BioSciences’ UltraShearTM technology. Methods: CBD nanoemulsion (2%) was provided by Pressure BioSciences, Inc. (South Easton, MA), and CBD pharmacokinetic parameters were evaluated in male Sprague-Dawley rats using LC-MS/MS technology. Results: Bioavailability of orally delivered CBD UltraShear nanoemulsion was calculated to be 18.6% at 6 h and 25.4% at 24 h. While oral-GI bioavailability is unsurprisingly limited by first-pass metabolism, it is nonetheless notable that CBD bioavailability for oral-GI UltraShear nanoemulsion CBD is roughly 3–4x higher than the typical bioavailability for oral-GI CBD delivered in oil solution or conventional edible formats. Conclusion: This study has provided a compelling demonstration of unprecedented speed and efficiency of oral-GI CBD absorption of CBD UltraShear nanoemulsions, achieving 10% of levels achieved for direct IV injection within 30 min and 80% of IV levels in 24 h. Notably, within just the first hour post-administration, the bioavailability of oral CBD from UltraShear nanoemulsion formulation exceeded the typical 6% total CBD oral bioavailability benchmarks reported for CBD edibles and ultimately achieved 3–4X these levels within 6–24 h.