OBJECTIVE: This study is a systematical review regarding the glaucoma treatment with drug-loaded contact lenses. The effectiveness and safety about that were summarized, which providing effective suggestions and guidance for clinical research. METHODS: The studies published up to May 1, 2024 on the treatment of glaucoma with sustained-release contact lenses were searched from CNKI, Wanfang Data, VIP, PubMed, Embase, Cochrane Library, and Medline. CAMARADES was used to evaluate literature quality. The safety, endpoints of intraocular pressure reduction (IOPR) and duration of intraocular pressure (IOP) decline during glaucoma treatment were analyzed by means of qualitative and quantitative methods. The protocol registration number is CRD42024487157. RESULTS: 47 studies were included. In clinical trials, glaucoma patients showed a 50% reduction in IOP and no corneal tissue destruction after wearing contact lenses. In animal experiments, the endpoint IOPR [MD = 0.58, 95%CI (0.37, 0.80), P <
0.00001] of the medicated contact lenses group was significantly better than that of the eye drops group. Subgroup analysis showed that contact lenses loaded with timolol (TML), with TML + dorzolamide, and with TML + latanoprost, which compared to eye drops, had a better effect on reducing IOP, while contact lenses loaded with puerarin, latanoprost, and TML + bimatoprost showed no statistical difference. Most studies demonstrated the duration of IOP reduction and drugs release in vitro for ≥3 days during contact lenses treatment. CONCLUSION: Most drug-loaded contact lenses exhibit excellent effectiveness and safety. The nanoparticle-loaded contact lenses containing TML for glaucoma treatment is recommended in future clinical research.