Abstract: Pinelliae Rhizoma (PR), known as Banxia in Chinese, Hange in Japanese, and Banha in Korean, is a renowned herbal medicine in East Asia derived from the dry tuber of Pinellia ternata (Thunb.) Breit. (PT). It is extensively utilized in dispensing granules, classical prescriptions, and herbal formulas to treat various conditions, including cough, infection, phlegm, nausea, asthma, and inflammation. Despite numerous studies on PR and its classical prescriptions over recent decades, a comprehensive synthesis of available evidence regarding its multifunctional roles and therapeutic potential is lacking. This review aims to address this gap by examining emerging evidence from metabonomics, preclinical studies, and clinical trials, while exploring potential trends and prospects for future research. A systematic literature search was conducted across six electronic databases, including PubMed, Web of Science, Scopus, ScienceDirect, Wanfang, and China National Knowledge Infrastructure, to identify relevant articles on PR published until March 2023. PR contains 107 compounds with diverse pharmacological activities, including anti-inflammatory, immune regulatory, anti-viral, anti-cancer, anti-asthma, antitussive and expectorant, antioxidant, anti-obesity, anti-atherosclerosis, anti-microbial, emetic and anti-emetic, anti-convulsant and anti-epileptic, sedative and hypnotic, learning and memory enhancement, and anti-depressant effects. Metabonomic studies suggest that raw PR may exhibit cardiotoxicity and pregnancy toxicity while showing no apparent hepatorenal toxicity. However, limited pharmacokinetic investigations on PR constrain its clinical translation. Furthermore, clinical safety data on PR is scarce, with only four clinical trials assessing its positive effects in pediatric epilepsy, nausea and vomiting, soft tissue injury, and chronic sinus tract. This review aims to enhance understanding of PR and provide valuable information and recommendations for further research and development of herbal medicine.