Background and Aims Several recent studies have investigated the relationship between telomere length and substance use disorders with inconsistent results. We aimed to assess this association and to identify moderators of the relationship. Methods Systematic review and meta‐analysis. Selection criteria were observational studies reporting telomere length in people with a substance use disorder compared with a control group. Studies focused solely on nicotine addiction, employing other study designs, and non‐human studies were excluded. Study selection and data extraction were independently conducted by two researchers following a standardized protocol and included studies until December 2019. Standardized mean differences were used as the effect size index [d; 95% confidence interval (CI)] and random‐effects models were used for the meta‐analysis. Cochran's Q‐statistic, I2 index, visual inspection of the forest plot and a 95% prediction interval were applied to verify study heterogeneity. Subgroup analyses and meta‐regressions were conducted to explore heterogeneity. Small study effects were examined using the ‘funnel plot’, the Egger test, Duval & Tweedie's trim‐and‐fill method and the precision‐effect test–precision‐effect estimate with standard error (PET‐PEESE) method. The risk of bias and the quality of evidence were assessed. Results Ten studies (12 analysis units with 2671 cases and 4532 controls) met the selection criteria. An overall effect size of moderate magnitude was found (d+ = −0.63; 95% CI = −1.00 and −0.26; P = 0.0008). A potential small study effect was detected, as well as large heterogeneity between studies (Q‐statistic P < 0.001, I2 = 97.3%). Selection of controls, reporting laboratory quality control procedures and total sample size significantly affected the effect size. The quality of the evidence was very low, based on risk of bias analysis and the grading of recommendations assessment, development and evaluation (GRADE) system. Conclusions People with substance use disorders appear to have shorter telomere length than controls; however, this finding should be interpreted with caution due to the poor quality of the evidence.