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Acceptance and Commitment Therapy (ACT) has been demonstrated as effective in improving psychological well-being in several clinical domains, but there is no evidence regarding the parents of children with Autism Spectrum Disorder (ASD). In this randomized controlled trial, we evaluated the efficacy of the ACT matrix behavioral protocol in comparison to the Parent Training (PT) program, measuring several primary and secondary outcomes prior to and following treatments. Twelve parents were randomly and equally assigned to two demographically matched groups wherein individuals underwent 24 weekly meetings of ACT protocol (experimental group) or conventional PT (control group). Parents enrolled in the ACT protocol demonstrated significant improvement in psychological flexibility, awareness states, personal values in everyday life, and parental stress, whereas reduced scores were elicited in parents’ perceptions of their child’s disruptive behaviors. The results of this randomized controlled trial, if repeated with a large number of subjects, could open the way to include ACT protocols in daily practice to support the development of new parenting skills.