Dietary supplement (DS) use among adults is on the rise. This growing trend in DS use mirrors the quick and exponential growth of the fitness industry. The fitness industry focuses on the “appearance of health”, although some individuals focus on their appearance over and above their health. As a result of this focus on appearance, certain aspects of this unregulated industry promote unhealthy standards of beauty and an increase in negative body image, and influences at-risk youth to engage in dangerous practices such as extreme diet and exercise routines, or the misuse of dietary supplements. All of these factors have been linked to appearance and performance enhancing drug use, which is associated with substance use in athletes and non-athletes. This study sought to explore the role of gender as it pertained to dietary supplement use, specifically how gender differences amongst predictors of DS use (including BMI, physical activity, and body image) were associated with overall substance use in college students. The relationship between current DS use and other substance use was also examined. Students recruited from ASU fitness centers completed a survey which included questions on demographics, height and weight to calculate BMI, and several published, standardized questionnaires used to measure drug use, physical activity, body image, steroid and ephedrine use and attitudes, and dietary supplement use. There were significant gender differences in DS use as well as predictors or DS use. Controlling for demographic information, energy enhancing DS use and knowing someone who used steroids increased the likelihood an individual intended on using steroids in the future. Body image was not related to substance use in males, and physical activity mediated the relationship between DS use and substance use in males. While body image was associated with substance use in females, neither physical activity nor body image mediated the relationship between DS use and substance use in females.