Objective: Assess and evaluate the different indicators of oral health-related quality of life (OHRQoL) among patients treated with clear aligners (CAs) versus those treated with conventional fixed orthodontics (FAs). Methods: An electronic search was performed on the database is Web of Science, Scopus, and Embase databases. Randomized and non-randomized control trials, cross-sectional, prospective cohort and retrospective trials were included. Quality was assessed with risk of bias tool and risk of bias in non-randomised studies. Meta-analyses were performed with random effects models, estimating the standardized and non-standardized mean differences, odds ratio and risk ratio as the measure of effect. The effect on time was determined using a meta-regression model. Results: Thirty one articles were included in the qualitative synthesis and 17 in the meta-analysis. CAs had a significantly lower negative impact on QoL, with an “important” effect size, while the influence of time was not significant.Periodontal indicators plaque index (PI), gingival index (GI), probing depth (PD), and bleeding on probing show significantly better values in patients treated with CAs, with moderate to large effect sizes. PI and GI have a significant tendency to improve over time. In microbiological indicators, CAs present a lower biofilm mass without differences in the percentage of patients with high counts of Streptococcus mutans and Lactobacilli bacteria. The risk of white spot lesion onset is ten times lower in carriers of CAs. Conclusions Patients wearing CAs show better periodontal indicators, less risk of white spot development, less biofilm mass and a better QoL than patients with FAs.