This systematic review aimed to determine the effects of the interproximal enamel reduction (IPR) techniques used in orthodontics. Six databases were searched: PubMed, Scopus, Web of Science, Dentistry & Oral Sciences Source, Science Direct, and Clinical Trials. Grey literature was sourced from Google Scholar. The risk of bias was assessed by Risk of Bias 2, Newcastle-Ottawa Scale, and Robins-I depending on the design of the evaluated study. Additionally, the quality of the included studies was determined using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. This systematic review included randomized clinical trials, non-randomized clinical trials, and observational studies with a control group that reported the effects of IPR for orthodontic purposes on the teeth and periodontium. Case reports, in vitro, and in vivo studies were excluded. Eight clinical studies match the eligibility criteria. As result, no demineralization of the enamel, no increase in caries incidence, no periodontal changes or dental sensitivity were found after IPR. Also, considering the duration of orthodontic treatment, IPR resulted in a quicker technique than dental extractions. At the risk of bias assessment, all observational studies showed low risk, the non-randomized clinical trial had a critical bias, and all randomized clinical trials exhibited some concerns. The overall quality of the studies was found between low to very low. After the analysis of the data from included studies, it was concluded that the IPR procedures could be useful to treat dental crowding in orthodontic clinical practice without negative effects. However, more randomized controlled clinical trials with a longer follow-up time and high-quality studies are required to generate robust statements.