Modern epidemiological and interventional studies have demonstrated that various bioactivities including antioxidant, antiproliferative, immune-regulatory, hormonal-regulation abilities and neuro-/hepato-/cardioprotective effects result from consumption of a phenolic-rich diet. The health benefits of ingesting phenolics are greatly dependent on their bioaccessibility and bioavailability in the digestive tract and circulatory system. This contribution attempts to review the bioaccessibility and bioavailability of phenolic compounds by focusing on the body’s internal mechanism including digestion, absorption, transport, modification, excretion, and colonic fermentation. The bioaccessibility and bioavailability of different phenolics vary depending on the physical condition of an individual, including digestive/absorptive/metabolic/response capability and effective dose. External factors such as processing methods and interaction with various food matrices also play a vital role on the bioavailability of dietary phenolic compounds. On the other hand, some novel phenolics have been synthesized to enable them rendering new bioactivities. The key internal factors influencing the bioaccessibility and bioavailability are also reviewed in this contribution. In addition, suggestions have been made for future measurement and assessment of bioavailability, together with prospects for food/nutraceutical/pharmaceutical application of novel phenolics.