Driving under the influence of drugs poses risks for traffic safety. Most research attention has been focused on the most prevalent drugs of abuse, such as alcohol, illegal drugs, and prescription drugs with high abuse potential. The objectives of this study were to determine the types of drugs used by convicted DUI offenders on the day of their arrest, prevalence of poly-substance use, and offender characteristics associated with different drug use patterns. Data were collected from 6,339 individuals enrolled in the court-mandated Mississippi Alcohol Safety Education Program. After alcohol, cannabis was the most frequently used substance, followed by sedative medications and prescription analgesics. Among poly-substance users, 78.4% reported combining alcohol with other drugs. Findings could be used to inform public education campaigns, law enforcement training, and highway safety policies about the prevalence of combining alcohol with other drugs, as well as how poly-substance use further impairs traffic-related risks.