The prevention of blindness from glaucoma requires multiple treatments to lower intraocular pressure. Here, human contact lenses are modified with highly porous metal-organic frameworks with sustained release of brimonidine for prolonged glaucoma treatment. Various metal-organic frameworks were screened for their attachment to lenses, loading with brimonidine, and drug-release properties. Optimized therapeutic ocular lenses conjugated with MIL-101(Cr) frameworks maintain optical transparency and power. Coating of lenses with MIL-101(Cr) nanoparticles reduced brimonidine washout with tears and ensured a gradual and localized release of the drug into the eyeball through the cornea. The hybrid lenses provided a 4.5-fold better decrease in eye pressure, compared by area under the curve (AUC) value to a commercially available brimonidine tartrate solution. Therapeutic lenses did not induce any notable eye irritation or corneal damage in vivo. The newly developed hybrid lenses are expected to provide a robust platform for the therapy and prevention of various ocular diseases. © 2024 Elsevier B.V., All rights reserved.