Oxymatrine is a quinazine alkaloid extracted from Sophora flavescens with various therapeutic effects such as organ- and tissue-protective, anti-inflammatory, anti-cancer, and anti-viral effects. In this review, we summarize the protective effects of oxymatrine on damaged organs and tissues by analyzing both in vivo and in vitro studies. The mechanisms of protective effects of oxymatrine are mainly related to its anti-inflammatory, anti-oxidative stress, anti- or pro-apoptotic, anti-fibrotic, metabolism-regulation, and anti-nociceptive functions. In addition, a variety of signal pathways, cells, and molecules are influenced by oxymatrine, and by these comprehensive actions, maximum therapeutic effects can be achieved. Furthermore, we summarize the protective effects in clinical studies and adverse effects of oxymatrine. It is believed that through more in-depth animal experiments and standardized clinical research, oxymatrine holds a bright future in the process of organ and tissue protection and has a significant therapeutic promise to translate from bench to bedside.