Commercial drivers often engage in long and irregular working hours, and as such suffer back pain, fatigue, stress and thereafter use some psychoactive substance to cope with their job. Even though most studies on substance use have been on general population, limited information is available on the use of substance and roles of socio-demographic factors among commercial drivers. This study therefore examined the roles of socio-demographic factors (age, years of driving, gender and social support) in substance use among commercial drivers in Ibadan, Nigeria.The study employed a cross-sectional design and purposive sampling technique to recruit 250 commercial drivers. A structured questionnaire was used to gather information on socio-demographic information, social support and substance use from the participants. Data were analyzed using descriptive statistics, correlation, Analysis of Variance and Independent t-test analysis. Results showed that years of driving significantly have a positive correlation with substance use. However, duration and hours spent on the driving did not have a significant independent relationship with substance use. Younger participants significantly engage more in substance use than older individuals. Similarly, female participants significantly engage more in substance use than male drivers. Additionally, participants with high social support mostly engage in substance use than participants with low social support. The study concluded that years of driving, age, gender and social support network of the drivers significantly plays an influencing roles in substance usage among commercial drivers in Ibadan. The study recommends that, in the organized substance use and abuse preventive program for drivers, the consideration for drivers’ socio-demographics factors is quite imperative, especially as more females and younger individuals with more social support are getting more involved in substance use.