Objectives: The objectives of this study were to explore the association between complementary and alternative medicine (CAM) use as reported by youth, and parents' and children's reported quality of life in youth with diabetes.Design: The study design was a cross-sectional survey.Setting: Youth in Washington State participated in the SEARCH for Diabetes in Youth study, a national, multisite epidemiological study designed to assess the prevalence and incidence of diabetes in U.S. youth. Surveys assessing CAM utilization were mailed in January and April 2006.Participants: One thousand four hundred and thirty-nine (1439) youth were mailed a CAM survey. The final sample consisted of 467 youth with both CAM survey results and quality-of-life data.Outcome measures: Difference in mean scores on Pediatric Quality of Life Inventory (PedsQL) between CAM users and nonusers overall, and specific CAM therapies were the outcome measures.Results: Of the 1439 participants approached, 587 (40.8%) returned the CAM survey. In adjusted analyses, children reported any CAM use as associated with more barriers to treatment (difference in mean scores −3.48, 95% confidence interval [CI] −6.65, −0.31). Children following a CAM diet reported higher quality of life (PedsQL Core Total difference 4.01, 95% CI [0.10–7.91]; Core Psychosocial difference was 6.45, 95% CI [1.95 to 10.95]), but those using stress-reduction activities reported poorer quality of life (Diabetes Total difference −4.19, 95% CI [−8.35 to −0.04]). Parent-reported quality of life was lower for children who used “other supplementsâ€? (Core Total difference −6.26, 95% CI [−11.29 to −1.24]; Core Psychosocial difference was −5.92, 95% CI [−11.65 to −0.19]).Conclusions: CAM diets were associated with increased quality of life in youth with diabetes, whereas supplement use and stress-reduction activities were associated with decreased quality of life. The temporal sequence between CAM use and quality of life requires further study.