The aim of this study was to examine the effect of brief cognitive-behavioral (C-B) intervention on improving confidence in managing situations related to heroin and methamphetamine (MAMP) use in drug users. The subjects in the intervention group received a five-session C-B intervention, which focused on the acquisition of skills aimed at helping the subject to reduce drug use. The subjects in the intervention and control groups completed pretest and posttest assessments to determine the changes of confidence in managing situations related to drug use. A total of 70 subjects (40 heroin and 30 MAMP users) and 75 subjects (38 heroin and 37 MAMP users) in the control group completed pretest and posttest assessments. The results revealed that among heroin users, the intervention group had greater improvement in confidence to manage interpersonal situations related to heroin use than did the control group, but there was no difference in the improvement in confidence to manage intrapersonal situations between the two groups. Furthermore, MAMP users in the intervention group showed greater improvement in confidence to manage both intrapersonal and interpersonal situations related to MAMP use than the control group. The present study confirmed the efficacy of brief C-B interventions in improving confidence in ability to resist urges to use heroin and MAMP in stressful interpersonal situations and to use MAMP in intrapersonal situations. The possible explanations for the ineffectiveness of brief C-B interventions to improve confidence in managing intrapersonal situations related to heroin use are discussed.