Substance use is not only affected every part of the abuser's life as social life, family life, work productivity, physical health, and personal relationships but also affected the community. Patients with substance use are experiencing problems related to non-assertive and aggressiveness. Aim: To examine the effect of life skills training on assertiveness, self-esteem, and aggressive behavior among patients with substance use disorders. Methods: A quasi-experimental design (one group pre/ post-test) was used to achieve the aim of the study. The study was conducted at an addiction outpatient clinic at The Psychiatric and Addiction Treatment Hospital in Mit-Khalf at Menoufia, Egypt. A purposive sample of 74 male patients with substance use disorders was included. Results: There was a highly statistically significant improvement in both self-esteem and assertiveness skills among the participants after life skills training than before at p < 0. 001, and there was a highly statistically significant reduction in aggressive behavior among the participants after the life skills training than before at p < 0. 001. Also, there was a statistically significant negative correlation between self-esteem, assertiveness skills, and total aggression after life skills training at p = 0.016, 0. 031. Conclusion: Life skills training significantly improved self-esteem, assertiveness, and decreased aggressive behavior among patients with substance use disorders.