Game-based virtual reality phone applications can create a realistic environment to prepare for clinical applications and improve students' knowledge of and compliance with standard precautions. An experimental study was performed among 126 nursing students' from the third and fourth nursing levels to determine the effect of online education and game-based virtual reality phone applications related to standard precautions. Students were divided randomly into two groups; the experimental group used online education and game-based virtual reality phone applications, while the control group used traditional education. The study was performed between July and August 2019 to prevent clashes with lectures and midterm and final examinations. A tool package including knowledge, attitude, and compliance with standard precautions was used in pre-and post-tests among nursing students. The results showed that the knowledge of, attitudes towards, and compliance with standard precautions differed between the two groups. The performance of the experimental group of nursing students significantly improved with online instruction and game-based virtual reality phone applications. This study demonstrated the effectiveness of online education and game-based virtual reality phone application among nursing students.