Background: Drug rehabilitation requires efforts to manage the participants’ stress, one of which is through psycho-education. Spiritual Emotional Model (SPIEM) dhikr is one of the psycho-education that can be given as part of rehabilitation for drug abusers. Purpose: This study aims to determine the effect of SPIEM dhikr on cortisol and immunoglobulin G (IgG) levels of drug abusers during rehabilitation programs. Patients and methods: This research used a quasi-experimental design with multiple intervention designs using a confirmatory factor analysis (CFA) approach. The affordable population that was also used as all subjects in this study were 31 police officers who underwent rehabilitation at Prof. Awaloedin Djamin Bhayangkara Hospital, Semarang, Central Java, Indonesia. The intervention of SPIEM dhikr consists of three phases for 3 weeks with 3 different dhikr methods, jaher, sirr and ruh/fi’ly, respectively. Each phase is carried out for 7×90 minutes/day. Cortisol and IgG levels were measured in the blood serum before and after the intervention. Results: SPIEM dhikr intervention for 3 weeks showed a significant effect (p<0.05) on decreasing cortisol levels from 107.65±7.43 ng/ml (before the intervention) to 77.84 ±3.99 ng/ml (after the intervention). IgG levels of the 31 subjects were significantly increased (p<0.05) from 80,61±4.66 ng/ml to 92,97±6.82 ng/ml after 3 weeks of intervention of SPIEM dhikr. Conclusion: Psychoeducation using SPIEM dhikr improves the stress and immunology responses of drugs abuser thus, it can be recommended as a rehabilitation program for drug abusers.