Depression is one of the most common psychiatric disorders and a mood disorder that manifests itself with symptoms such as low mood, loss of feeling, emptiness, mental and motor slowness, sadness, hopelessness, boredom, loneliness, they show guilt and inability to concentrate and thoughts related to death. The aim of the present study was the effectiveness of spiritual therapy on negative self-esteem thoughts and life satisfaction of university depressed students. The method of this research was semi-experimental with a pre-test and post-test design with a control group. The statistical population of this research included all depressed male and female students. The sample of this research included 36 depressed students (18 students in the experimental group and 18 students in the control group) who were selected by simple random. The process of selecting the sample was as follows: first, the Beck depression questionnaire was administered among students, and among the 66 students who scored above 20 (cut point) and based on the entry criteria, 36 were randomly selected into two experimental and control groups. (each group consist of 18 individuals). The experimental group was exposed to 10 sessions of spiritual training, and during this time, the control group did not receive any treatment. Beck depression questionnaire, negative spontaneous thoughts questionnaire and life satisfaction scale were used to collect data. The results of multivariate analysis of covariance (MANOVA) showed that spiritual therapy training was associated with a decrease in self-negative thoughts and an increase in life satisfaction of depressed students (p<0.001). Based on the findings of this research, it can be concluded that spiritual therapy actually reduces negative emotions such as depression through secret and need with God and solitude with the Almighty, and as a result improves life satisfaction in a person.