Methadone and buprenorphine can affect the psychological symptoms and cognitive functioning of substance users. This study aimed to compare psychological symptoms and neuropsychological functioning in methadone maintenance patients (MMP), buprenorphine maintenance patients (BMP), current opioid users, and healthy subjects. One hundred and twenty participants (30 in each group) matched for age, sex, and education completed the Symptom Checklist-90-Revised (SCL-90-R) and a battery of neuropsychological tests including the Wisconsin Card Sorting Test (WCST), Wechsler Memory Scale (WMS-IV), and Stroop Color-Word Test (SCWT) assessing executive functioning, working memory, and attention, respectively. Overall, opioid users showed more severe psychological symptoms compared to healthy subjects. MMP and BMP had intermediate scores in SCL-90-R subscales; however, BMP had fewer severe symptoms compared to the MMP group. In terms of cognitive functioning, healthy subjects and current users demonstrated the best and the worst performance, respectively. Also, BMP outperforms MMP on executive functions and attention. However, the MMP had a better performance in WMS (visual memory). Patients receiving maintenance treatment had fewer psychological symptoms and better cognitive performance compared to opioid users. BMP had a better profile in all psychological symptoms and better performance in executive functions and selective attention compared to the MMP suggesting buprenorphine may be a better choice for the treatment of opioid-dependent patients.