Soybean is an important grain and oil crop. In China, there is a great contradiction between soybean supply and demand. China has around 100 million ha of salt-alkaline soil, and at least 10 million could be potentially developed for cultivated land. Therefore, it is an effective way to improve soybean production by breeding salt-alkaline-tolerant soybean cultivars. Compared with wild soybean, cultivated soybean has lost a large number of important genes related to environmental adaptation during the long-term domestication and improvement process. Therefore, it is greatly important to identify the salt-alkaline tolerant genes in wild soybean, and investigate the molecular basis of wild soybean tolerance to salt-alkaline stress. In this review, we summarized the current research regarding the salt-alkaline stress response in wild soybean. The genes involved in the ion balance and ROS scavenging in wild soybean were summarized. Meanwhile, we also introduce key protein kinases and transcription factors that were reported to mediate the salt-alkaline stress response in wild soybean. The findings summarized here will facilitate the molecular breeding of salt-alkaline tolerant soybean cultivars.