Exploring medicinal plants for their natural products to benefit humanity has been a practice since ancient times. Berberis aristata, also known as tree turmeric or Indian barberry, has a dominant spot in conventional medicine for 2500 plus years. In the latter years, this particular species has gained prime attention in pharmaceutical zone due to its scarcity. The plant and its formulations are used to treat numerous human health threats including cancer, diabetes, diarrhea, wound relieving, infections of eyes and ears, gynecological disorders, and HIV-AIDS. The bioactive compounds present in B. aristata are found to contain anti-inflammatory, antioxidant, and anti-microbial properties. The plant is critically jeopardized species of Indian Himalaya due to the collection of its roots at a large scale for obtaining berberine alkaloid and its conservation is of great concern. At present, isolation of endophytic entities from remedial plants revolutionized the path of discovering drugs from medicinal plants. Endophytes can produce the same bioactive as their host plant as well as another bioactive to address a variety of human health issues. The review examines the bioprospecting of B. aristata, a medicinal shrub from the family Berberidaceae, and its associated endophytes for the production of bioactive compounds with application to human health. Finally, the review provides a comprehensive outlook on the current status and future prospects of bioprospecting B. aristata and its endophytes to combat future human health threats is an exciting area of research that should be further explored.