Background: Cognitive impairment in drug users is a marker for predicting recurrence and poorer adherence to treatment. The purpose of this study was to compare the cognitive function in three groups of methadone users methadone maintenance treatment (MMT), compared to methadone and methamphetamine (MAMP) users (MMT + MAMP) and healthy people (control group). Methods: Three groups of 90 people including 30 users of MMT, 30 users of MMT + MAMP, and 30 healthy persons participated in this cross-sectional and purposeful study. The study was performed on outpatients of MMT Clinic of Psychiatric Hospital in Kerman, Iran. The demographic and related data questionnaire was filled out. In addition, Persian version of the Brief Assessment of Cognition in Schizophrenia (BACS) was used to assess cognitive function. Findings: The mean of total number of scores and all BACS subscales were significantly better in control group than the other two groups of patients. Moreover, not only the mean of total number of BACS was significantly different between two substance abuser groups, but also there was a significant difference between them on verbal memory, digit sequencing, and token motor test, with MMT + MAMP group performing worse than MMT group. Conclusion: Concomitant use of opioids and stimulant substance such as MAMP results in cumulative toxic effect of them on brain and cognitive functions.