<p>To evaluate the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) for cervical squamous intraepithelial lesion (SIL). We systematically searched PubMed and other databases to compare the effectiveness of 5-ALA PDT with observation, ablation, and conization. Outcomes included overall response rate (ORR), complete remission (CR) rate, HPV clearance rate, and other relevant endpoints. Single-arm analyses were additionally performed by lesion grade. A total of 3,354 patients were included across 19 studies. The ORR with PDT was significantly higher than with observation (OR = 10.27, 95% CI: 3.87–27.27) and ablation (OR = 2.57, 95% CI: 2.00-3.30), with no significant difference compared with conization. At 6 months, HPV clearance rate was significantly higher with PDT than with observation (OR = 11.47, 95% CI: 3.16–41.68) and ablation (OR = 1.46, 95% CI: 1.01–2.13), but was comparable to conization. PDT also associated with a lower risk of progression than observation (OR = 0.19, 95% CI: 0.11–0.34) and a lower recurrence rate than ablation (OR = 0.30, 95%CI 0.14–0.63). ORR was 0.86 (95% CI: 0.83–0.89) in LSIL and 0.91 (95% CI: 0.87–0.94) in HSIL, with a significant difference between groups (<i>P</i> = 0.0289). 5-ALA PDT for cervical SIL improves ORR and HPV clearance compared with observation and ablation, with efficacy comparable to conization and only mild adverse events. It is effective across lesion grades, with slightly better responses in HSIL.</p>