With the development of society and the progress of science and technology, the demand for applied talents is increasing. In this background, the teaching reform of applied undergraduate universities is particularly significant. As a widely applied mathematics course, the teaching reform of probability theory and mathematical statistics aims to enhance students’ practical application ability and innovation ability. This paper discusses the teaching reform strategies in probability theory and mathematical statistics courses in applied undergraduate colleges, including the integrated teaching of science and reality, the teaching of rethinking, and case teaching. Through the integrated teaching of science and practice, theoretical knowledge is combined with practice to enhance students’ data analysis ability; through the teaching of focusing on ideas, the understanding of the ideological methods of probability statistics is emphasized rather than the mere derivation of theorems; through the teaching of case studies, practical problems are combined with theoretical knowledge to enhance students’ sense of application and problem-solving ability. Studies have shown that these reform measures can significantly improve students’ academic performance and practical ability, and provide strong support for the cultivation of application-oriented talents. Future teaching reforms need to constantly summarize experiences and improve measures to adapt to the changing social needs and technological progress.