Purpose: The purpose of this study was to identify the effects of the Gratitude Enhancement Program on self-esteem, interpersonal relationships, gratitude disposition, subjective happiness, stress index in patients with chronic schizophrenia. Methods: The research was designed for a nonequivalent control group before and after the test design. The subjects of this study were 29 patients in the experimental group and 28 patients in the control group. The Gratitude Enhancement Program was conducted three times a week for a total of nine sessions. Data were collected with questionnaires and measured with autonomic nervous system response (stress index) and was analyzed by t-test, chi-square test, Fisher’s exact, and repeated measures ANOVA with the SPSS/WIN 23.0 program. Results: There are no significant differences in the homogeneity test of a dependent variable between groups. The experimental group showed significant higher scores of self-esteem, interpersonal relationships, gratitude disposition, and subjective happiness than the control group. There was no significant difference in the stress index between two groups. Conclusion: Based on the results of this study, this Gratitude Enhancement Program can be a good nursing intervention to improve self-esteem, interpersonal relationship, gratitude disposition, and subjective happiness for chronic schizophrenia patients.