Substance use behaviors often emerge during adolescence, and adolescents with type 1 diabetes (T1D) may be at risk for engaging in traditional substance use (eg, alcohol, tobacco, and illicit substances) as well as a unique form of substance use: insulin misuse. The purpose of this exploratory study was to examine substance use and insulin misuse in adolescents with T1D. Sixty adolescents aged 12 to 20 years with T1D (n = 60) completed surveys on substance use, insulin misuse, and diabetes self-management during a routine diabetes appointment. Demographic measures were summarized by mean (SD) or percentage. Prevalence of substance use and insulin misuse was calculated and stratified by demographic and clinical characteristics. Two-sample t test (continuous variables) and chi-square analysis (categorical variables) determined statistically significant differences. The prevalence of ever using substances was 36.7%, and that for ever misusing insulin was 19%. Older participants (17.1 ± 1.8 vs 15.6 ± 1.9 years; P < .01) and those with depression (31.8% vs 7.9%; P = .02) were more likely to use substances. Disordered eating behaviors were the most frequently reported reason for insulin misuse. Self-harm intent was reported by one-third of insulin misusers. Substance use and insulin misuse were not related to glycemic control or diabetes self-management behaviors. The diabetes care team should be aware that substance use and insulin misuse are common in adolescents with T1D. Screening for these risky behaviors is critical in those who are older or have mental health disorders. Effective education, prevention, and treatment strategies targeted at these behaviors are needed to improve the overall health of this population.