Malocclusion may affect interpersonal relationships, self-esteem (SE), and psychological well-being, weakening patients' psychological and social activities. Several studies investigated the effect of orthodontic treatment on these social and psychological aspects, such as SE. However, the direct relationship between SE and orthodontic treatment has not yet been confirmed. This systematic review aimed to evaluate the existing evidence in the literature concerning the influences of orthodontic treatment on patients' SE systematically and critically. An electronic search in the following databases was done in September 2022: PubMed®, Web of Science™, Scopus®, Embase®, GoogleTM Scholar, Cochrane Library databases, Trip, and OpenGrey. Then, the reference list of each candidate study was checked for any potentially linked papers that the electronic search might not have turned up. Inclusion criteria were set according to the population/intervention/comparison/outcome/study design (PICOS) framework. For the data collection and analysis, two reviewers extracted data separately. The risk of bias 2 (RoB-2) and the risk of bias in non-randomized studies (ROBINS-I) tools were used to assess the risk of bias for randomized controlled trials (RCTs) and non-RCTs, respectively. The grading of recommendations assessment, development and evaluation (GRADE) approach was employed to evaluate the quality of the evidence for each finding. Sixteen studies (five RCTs, seven cohorts, and four cross-sectional) were included in this review. Unfortunately, the results could not be pooled into a meta-analysis. Only six studies have reported an increase in SE after orthodontic treatment (P<0.05 in these studies). No agreement between the included studies was observed regarding the influence of fixed orthodontic treatment, gender, or age on SE. The quality of evidence supporting these findings ranged from very low to low. There is low evidence indicating that fixed orthodontic treatment can improve patients' SE. In addition, unclear data are available about the influence of patients' gender and age on SE after orthodontic treatment. Therefore, high-quality RCTs are required to develop stronger evidence about this issue.