Background Smile attractiveness is a primary factor for patients to seek orthodontic treatment, however, there is yet no systematic evaluation of this topic in the literature. Objectives To assess the current evidence on the effect of orthodontic treatment on smile attractiveness. Search methods Seven electronic databases (MEDLINE, Cochrane Library, Virtual Health Library, SCOPUS, Web of Science, Google Scholar and Embase) were searched on 14 September 2022. Selection criteria Studies evaluating smile attractiveness before and after orthodontic treatment or only after completion of orthodontic treatment. Data collection and analysis Extracted data included study design and setting, sample size and demographics, malocclusion type, treatment modality and method for outcome assessment. Risk of bias was assessed with the ROBINS-I tool for non-randomised studies. Random-effects meta-analyses of mean differences and their 95% confidence intervals (CIs) were planned a priori. Methods After elimination of duplicate studies, data extraction and risk of bias assessment according to the Cochrane guidelines, an evaluation of the overall evidence was performed. The included studies were evaluated based on the characteristics of their study and control groups and based on their main research question. Also, all outcome measures were standardized into a common assessment scale (0–100), in order to obtain more easily interpretable results. Results Ten studies were included in this review, nine of which were assessed as being at serious risk of bias and one at moderate risk of bias. The large heterogeneity between the included studies did not allow for a meta-analysis. Orthodontic treatment has a moderately positive effect on smile attractiveness. When compared to no treatment, orthodontic treatment with premolar extractions improves smile attractiveness by 22%. Also, surgical correction of Class III cases increases smile attractiveness by 7.5% more than camouflage treatment. No other significant differences were shown between different types of treatment. Conclusion Based on the available data, orthodontic treatment seems to moderately improve the attractiveness of the smile. There is significant bias in the current literature assessing the effect of orthodontics on smile attractiveness; therefore, the results cannot be accepted with certainty.