Objective To explore the application effect of organ system-integrated virtual simulation teaching in endocrine and metabolic disease nursing for undergraduate nursing students. Methods A quasi-experimental study with a nonconcurrent control design was conducted. Fifty-eight undergraduate nursing students learning endocrine and metabolic disease nursing in 2024 were selected as a control group, and 58 students learning in 2025 were regarded as an experimental group.The control group received traditional teaching model, while the experimental group received the organ system-integrated virtual simulation teaching model. Results Fifty-five students in the control group and fifty-six students in the experimental group completed the study.Compared with the control group, the experimental group showed significantly better in theoretical knowledge, practical skills, teaching satisfaction rate, and scored higher in the total scores of general self-efficacy, learning engagement and the vigor and dedication subscale scores after the teaching （all P＜0.05）. Conclusion Organ system-integrated virtual simulation teaching can improve learning outcomes in endocrine and metabolic disease nursing education, enhance students′ self-efficacy, and promote learning engagement.