Botulinum toxin A (BoNT/A) injections into the bulbospongiosus muscle have emerged as a novel treatment for lifelong premature ejaculation (PE), though efficacy remains controversial. This study evaluates BoNT/A’s efficacy and safety through a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and ISRCTN registry. We included randomized controlled trials, prospective, and retrospective studies, focusing on intravaginal ejaculation latency time (IELT) and adverse events. Four studies (three meta-analyzed) involving 263 patients were analyzed. BoNT/A increased IELT by 37.87 s at 1 month (MD, 37.87; 95% CI, −2.86 to 78.59;
p
= .07;
I2
= 96%), 11.52 s at 3 months (MD, 11.52; 95% CI, −16.91 to 39.94;
p
= .43;
I2
= 95%), and 2.41 s at 6 months (MD, 2.41; 95% CI, −9.19 to 14.00;
p
= 0.68;
I2
= 77%). Short-term IELT improvement was observed but lacked statistical significance (
p
> .05), with high heterogeneity (
I2
= 96%). Long-term effects diminished, suggesting declining efficacy. Adverse events occurred in 10.9% of patients, primarily erectile dysfunction (
n
= 5), and urinary disorders (
n
= 5). While current evidence does not definitively support BoNT/A’s efficacy, limited studies and methodological heterogeneity suggest that further research is warranted. Future studies should employ larger, multicenter designs, optimize injection methods, doses, and protocols, and identify suitable patient populations to validate BoNT/A’s clinical benefits.