While the effectiveness of parent-mediated interventions in the field of autism spectrum disorder is well documented, information on the experience of parents involved in parent-mediated interventions is limited. We performed a systematic review with qualitative evidence synthesis to explore the experience of parent-mediated interventions in parents of children with autism spectrum disorder. PubMed, Scopus, PsycINFO, CINAHL, and Sociology Collection were searched from the date of their creation until 25 February 2022. Qualitative studies reporting parents' experience of parent-mediated interventions were included. Two independent reviewers assessed the risk of bias. The findings of the selected studies were extracted and synthesized using the meta-aggregation method. The results are reported according to PRISMA and ENTREQ guidelines. A total of 23 studies were synthesized representing 345 participants. We found 34 categories that were summarized in four synthesized themes: barriers to implementation and logistical issues, feeling overwhelmed and stressed (a need for support), facilitators of implementation, and empowerment in the parent and improvement in the child. Parents' experience of parent-mediated interventions in autism spectrum disorder is balanced between positive outcomes for them and their child, emotional struggles, and some difficulties in implementing parent-mediated interventions. Based on these results, we propose new ways to improve implementation of parent-mediated interventions and research in the field.