Substance abuse is one of the most important social deviations, which is foundation of many social damages and problems at the community level. Every part of the substance abuser's life as social life, family life, work productivity, physical health and personal relationships is affected. Aim: The aim of the present study was to determine the effect of psycho-educational nursing program on social adjustment and self-esteem among substance abusers. Design: A quasi-experimental design (pre and posttest) was used to achieve the aim of the study. Setting: This study was conducted at the outpatient clinics for addiction at the Psychiatric Mental Health Hospital in Benha City, Qalubia Governorate, which is affiliated to General Secretariat of Mental Health in Egypt. Subject: A convenience sample of 40 substance abusers was included from the above setting for conduction of this study. Tools: Three tools were used for data collection. Tool 1- structured interview questionnaire was used to collect data about socio demographic and clinical characteristics of the studied sample. Tool 2- Social Adjustment scale (SAS) to assess social adjustment of different life domains among the studied sample. Tool 3- Self-esteem scale (SES) was used to assess self-esteem among the studied sample. Results: There was a highly statistically significant improvement in total score of social adjustment and total score of self-esteem between pre and post implementation of the program. Conclusion: The study demonstrated that psycho-educational nursing program had a positive effect on enhancement of social adjustment and self-esteem among substance abusers. Recommendations: A psycho educational program should be given for all substance abusers based on a treatment protocol during their hospitalization to enhance their self-esteem and social adjustment.