Objectives Previous meta-analyses suggested that mindfulness-based interventions (MBIs) may have beneficial effects on telomere length (TL) and telomerase activity (TA), two biological markers of cellular aging and cell stress. The present review aimed to provide the most comprehensive synthesis of the available evidence to date and tested a number of important effect moderators. Method Twenty-five studies (18 RCTs, 1 RCT and cohort study, 6 non-randomized studies) with 2099 participants in total were obtained with a systematic literature search, 10 studies had not been included in any previous meta-analysis. Effect sizes were aggregated with random-effects models, the risk of bias was evaluated with standardized checklists, and the most influential moderators were identified with a machine-learning approach. Results On average, MBIs had small-to-medium effects on TL (g = 0.23, 95% CI = [0.07, 0.39], p = 0.006) and TA (g = 0.37 [0.01, 0.73], p = 0.046), which, however, were driven by retrospective case–control studies with experienced meditators (TL) and by studies without control interventions and studies from Asia (TA). Most studies had an unclear risk of bias and low analytic power, and there was an indication of publication bias among the TL studies. Conclusions TL may not be a useful outcome to assess the efficacy of common MBIs. Effects on TA were smaller than previously assumed and may not be specific for MBIs; TA likely is increased by other active interventions as well. More high-quality and high-powered studies, which also apply open-science practices, are needed to move the field forward.