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Abstract Background The application of calcium phosphate (CaP)-based bone substitutes plays an important role in periodontal regeneration, implant dentistry and alveolar bone reconstruction. The incorporation of strontium (Sr) into CaP-based bone substitutes appears to improve their biological properties, but the reported in vivo bone repair performance is inconsistent among studies. Herein, we conducted a systematic review and meta-analysis to investigate the in vivo performance of Sr-doped materials. Methods We searched PubMed, EMBASE (via OVIDSP), and reference lists to identify relevant animal studies. The search, study selection, and data extraction were performed independently by two investigators. Meta-analyses and sub-group analyses were conducted using Revman version 5.4.1. The heterogeneity between studies were assessed by I2. Publication bias was investigated through a funnel plot. Results Thirty-five studies were finally enrolled, of which 16 articles that reported on new bone formation (NBF) were included in the meta-analysis, covering 31 comparisons and 445 defects. The overall effect for NBF was 2.25 (95% CI 1.61–2.90, p < 0.00001, I2 = 80%). Eight comparisons from 6 studies reported the outcomes of bone volume/tissue volume (BV/TV), with an overall effect of 1.42 (95% CI 0.65–2.18, p = 0.0003, I2 = 75%). Fourteen comparisons reported on the material remaining (RM), with the overall effect being -2.26 (95% CI − 4.02 to − 0.50, p = 0.0009, I2 = 86%). Conclusions Our study revealed that Sr-doped calcium phosphate bone substitutes improved in vivo performance of bone repair. However, more studies are also recommended to further verify this conclusion.