In this paper, we describe a simple method for constructing a micellar supramolecular hydrogel, composed of a low-molecular-weight methoxy poly(ethylene glycol) (M-n = 2000 Da) block polymer and alpha-cydoclextrin (alpha-CD), for topical ocular drug delivery. Adding aqueous block polymer micelles into an alpha-CD aqueous solution resulted in the formation of a micellar supramolecular hydrogel through host-guest inclusion. The effects of the drug payload, block polymer, and alpha-CD concentrations as well as the block polymer structure on gelation time were investigated. The resultant micellar supramolecular hydrogels were thoroughly characterized by X-ray diffraction, rheological studies, and scanning electron microscopy. The hydrogels exhibited thixotropic properties, which are beneficial to ocular drug delivery. In vitro release studies indicated that the alpha-CD concentration strongly influenced the release rate of diclofenac (DIC) from supramolecular hydrogel. The hydrogels showed relatively low cytotoxicity toward L-929 and HCEC cells and did not significantly affect the migration of the latter after 24 h incubation. The hydrogel was nonirritant toward the rabbit eye, as indicated by the Draize test, fluorescein staining, and histological observation. Nile Red labeled micellar supramolecular hydrogel showed that it could significantly extend the retention time on the corneal surface in rabbits, compared with a plain micellar formulation. In vivo pharmacokinetics indicated that the hydrogel could greatly improve ocular drug bioavailability, compared with that of micellar formulation. Our results suggest that the micellar supramolecular hydrogel is a promising system for ocular drug delivery.