The growing awareness of the harmful effects of synthetic drugs has led to the increased exploration of time-tested traditional alternative medicines. Interest in plant-based medicines is rising exponentially, as herbal remedies are perceived to be safer and have fewer adverse effects than many existing synthetic drugs. As a tropical country, India is blessed with a wide variety of tree species and traditional knowledge for their wise and sensible utilization. Tree bark is a potential raw material and a rich source of phenolic compounds. These compounds are synthesized and accumulated in the subepidermal layers of plant tissues exposed to stress and pathogen attack. Properties such as biodegradability, UV-shielding, and free radical scavenging activity make them suitable for medical, pharmaceutical, food, and beauty applications. Their antioxidant potential can be used as a supplement in the therapy of oxidative stress mediated diseases such as cancer, diabetes, and inflammation. For a long time, tree bark has been used without scientific verification. Thus, ongoing research activities are aimed at authenticating the traditional medicinal values of bark. We aim to systematically summarize the work on their traditional uses, phytochemical screening, and healing applications, which could favorably provide a perspective for further research. The chapter also explores the challenges associated with developing phenolic compounds from tree bark as therapeutic agents, including issues with bioavailability and toxicity. Further studies are proposed to explore tree bark to isolate novel active or synergistic compounds, investigate bioactivity, and clarify the mechanisms of action of its active principles, clinical trials, toxicity, and proper standardization to identify their full therapeutic potential for developing new multifunctional drugs and for using phenolic compounds as natural antioxidants.