This article aims to provide a comprehensive review of Cissus quadrangularis (CQ), which is a traditional medicinal herb and has a potential osteoprotective effect. CQ is a perennial climber of family Vitaceae that is commonly found in the hotter parts of India. It is most widely used in India for improving bone health and is well known as “hadjod.” It shows an anti-osteoporotic effect through different pathways mechanisms. It is natural matrices of excellence with proven bioactivity. Several cell line and animal studies demonstrated its protective nature against many diseases such as osteoporosis, arthritis, gastric ulcers etc. This review also highlights the phytochemicals identified to the date and related pharmacological applications. The discussion has also expanded to its oral formulations, which has been proven for its efficacy practically. However, the scientific information of CQ is not in the proper documentation for reference, and so availability of scientific knowledge of this climber is limited. Therefore, this review might be provided a platform to those who will be interested in studying further this herb, either for analyzing phytochemical profiling or its anti-osteoporotic usage. This is a crucial platform as several productive results have been reported on this herb, which likely to be beneficial for new drug discovery in future. Here we also discuss the bone remodeling and related factors influenced by the intake of CQ.