Empathy is an important and valuable tool in therapeutic communication. Improvement barriers of empathy in psychiatric nursing education are associated with challenges, such as stress due to negative attitudes toward psychiatric disorders. The current study aimed at comparing the effects of contact-based education and commitment and acceptance-based training on empathy toward mental illnesses among nursing students. In this clinical trial, 111 nursing students were selected using cluster and quota sampling methods in Mashhad, Iran. They were divided into 3 groups: (1) contact-based education (interpersonal contact among individuals with improved mental illnesses), (2) acceptance and commitment-based training, and (3) control group. The study tool was Jefferson Nurses Empathy Questionnaire, which was completed in 3 stages of pretest, posttest, and follow- up. Data were analyzed by repeated- measures ANOVA. There was no significant difference between contact-based education and acceptance and commitment-based training groups in increasing the average score of total empathy during pretest, posttest, and 1-month follow- up (p = 0/92). However, a significant difference was found between contact-based education and control group (p = 0/004) and between acceptance and commitment-based training and control group (p = 0/02). Both methods of contact-based education and acceptance and commitment-based therapy were effective in increasing the level of empathy into mental illnesses in nursing students.