Abstract: Biomacromolecules hold the promise of restoring sight for many patients with eye diseases. Unfortunately, hampered by various dynamic and static ocular absorption barriers, it is hard to deliver biomacromolecules into the eye safely and effectively. In clinical practice, biomacromolecules need to be administered via intraocular injection. However, frequent intraocular injection is usually associated with various side-effects and poor patient compliance. Development of ideal ocular drug delivery systems to achieve noninvasive administration of biomacromolecules, especially delivery to the posterior segment of the eye for treatment of fundus oculi diseases, has always been the unmet need for ophthalmology. This article reviews the physiologic barriers that hinder ocular absorption of drugs and recent progress in noninvasive ocular delivery of peptides, proteins, and genes in virtue of nanotechnologies, cell-penetrating peptides, and other physical strategies, in attempt to provide some reference for related research.