In this work, we developed a new class of branched polyrotaxane hydrogel made of 4-arm polyethylene glycol (4-PEG) and α-cyclodextrin (α-CD) using supramolecular host-guest interactions as a cross-linking strategy. Because of the dynamic nature of the non-covalent host-guest cross-linking, the resulting supramolecular α-CD/4-PEG hydrogels show thixotropic behavior and undergo a reversible gel-sol transition in response to shear stress change. We loaded the antiglaucoma drug brimonidine into the α-CD/4-PEG gel and found the drug release kinetics was controlled by shear stress. This thixotropic shear thinning property makes the supramolecular hydrogels highly attractive in drug delivery applications and suitable for preparation of injectable drug formulations.