Antipsychotic treatment in youth with autism spectrum disorder (ASD) is becoming increasingly common, placing individuals at risk for antipsychotic-induced weight gain and associated complications. Metformin hydrochloride, a biguanide medication FDA-approved for treatment of type-2 diabetes in youth, may hold promise for treatment of antipsychotic-induced weight gain in youth with ASD. In this report we assess the long-term impact of metformin on antipsychotic-associated weight gain in a naturalistic sample of 53 youth with ASD. Results indicate that treatment with metformin stabilized BMI z-score over a nearly 2 year mean treatment period. Further work is indicated to determine the safety and efficacy of metformin treatment in youth with ASD, as well as predictors of response as a treatment for antipsychotic-induced weight gain.