Optisol-GS is the most widely used pharmaceutical composition to preserve corneas for transplantation. This systematic review investigated the effects of different cold corneal storage media (CCSM) compared with Optisol-GS on the quality of stored corneas. The literature was searched throughout May 2022 on six databases and grey literature. Studies including corneas (population) exposed to distinct cold storage media (exposure) and Optisol-GS (comparison) that reported qualitative and/or quantitative parameters of cornea quality (outcome) were included. Methodological quality was assessed using ToxRTool. From 4520 identified studies, fourteen were included according to the eligibility criteria, comprising 769 evaluated cornea samples comparing Optisol-GS with commercial and noncommercial media. All studies showed good methodological quality. Experimental times ranged from 1–28 days, mainly using 4 °C as the preservation temperature. Viable endothelial cell density (ECD) and endothelial cell morphology (EC) were the most assessed parameters. ECD results for Cornisol were higher than Optisol-GS in 10 days (p = 0.049) and favored Cornea ColdTM up to 4 weeks (p < 0.05), which also showed better qualitative results. While the standardization of test protocols could improve comparisons, evidence indicates that most CCSM present similar performances on cornea preservation for transplantation at seven days, while some formulations may increase preservation at extended times.