The aim of this systematic review is to appraise the current evidence on the efficacy and safety of buspirone in core symptoms of autism spectrum disorder (ASD), co-occurring anxiety, and other associated symptoms. Major medical literature databases were searched for randomized controlled trials (RCTs), open-label trials, and any other relevant studies or clinical trials reporting on pediatric (age < 18 years) patients with ASD treated with buspirone for any reason. A total of 310 abstracts were screened, and six clinical trials were selected for inclusion. Out of these six clinical trials, two were RCTs (n=166 and 40), two open-label trials (n= 26 and 4), and one cross-over study (n= 1). We also included one retrospective chart review (n=31). Meta-analysis was not performed due to a lack of homogeneity in the two RCTs. Although most of the studies reported improved overall symptoms, they had different outcome measures. The quality of evidence available is low, and there is a need for higher-power studies in the future. Most studies suggested that buspirone was well tolerated and safe in pediatric patients with ASD. Based on the data, there is insufficient evidence to make conclusive recommendations on buspirone for improvement in core symptoms of ASD or cooccurring anxiety, irritability, or hyperactivity symptoms in the pediatric population. Given there are limited approved therapies for co-occurring anxiety, buspirone could be used as a safe off-label option due to the lack of behavioral activation and any serious adverse reactions.