Objective To systematically evaluate the efficacy and safety of letrozole combined with metformin in the treatment of polycystic ovarian syndrome (PCOS) infertility. Methods PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Chongqing VIP, Wanfang, and SinoMed were searched from establishment to December 31, 2022. The literature on randomized controlled trials of letrozole combined with metformin in the treatment of PCOS infertility were included. RevMan 5.4 software was used for meta-analysis. Results A total of 29 articles including 3226 subjects were included, with trial group of 1614 treated with letrozole combined with metformin, and control group of 1612 treated with letrozole alone. The meta-analysis results showed that the clinical pregnancy rate [relative risk (RR)=1.76, 95% confidence interval (CI) (1.61, 1.92)], induced ovulation rate [RR=1.22, 95%CI (1.17, 1.28)], and number of dominant follicles [mean difference (MD)=1.15, 95%CI (0.86, 1.43)] in the trial group were higher than those in the control group (P<0.05). The follicle growth time [MD=−5.41 d, 95%CI (−6.03, −4.80) d], estradiol level [MD=−7.57 pmol/L, 95%CI (−10.59, −4.56) pmol/L], luteinizing hormone level [MD=−2.27 U/L, 95%CI (−2.59, −1.95) U/L], testosterone level [MD=−1.29 nmol/L, 95%CI (−1.74, −0.85) nmol/L], fasting blood glucose level [MD=−0.91 mmol/L, 95%CI (−1.71, −0.65) mmol/L], fasting insulin level [MD=−25.93 pmol/L, 95%CI (−29.06, −22.80) pmol/L], insulin resistance index [MD=−1.40, 95%CI (−1.61, −1.19)], and the incidence of ovarian hyperstimulation syndrome [RR=0.44, 95%CI (0.22, 0.88)] in the trial group were lower than those in the control group (P<0.05). There was no statistically significant difference in follicle stimulating hormone level, incidence of adverse reactions, and spontaneous abortion rates between the two groups (P>0.05). Conclusion Existing evidence suggests that compared to using trazole alone, the combination of letrozole and metformin can improve ovulation induction and pregnancy outcomes in patients with PCOS infertility. The combination of the two drugs can reduce levels of estradiol, testosterone, and luteinizing hormone in patients, while effectively reducing the incidence of ovarian hyperstimulation syndrome.