Glaucoma is the second common cause of irreversible blindness worldwide associated with a progressive neurodegenerative disease of retinal ganglion cells (RGC). The major hypothetical mechanisms of the apoptosis of RGCs includes deprivation of neurotrophic factors, excitotoxicity mediated by the interaction of glutamate with NMDAR. This article reviewed current development of three kinds of neuroprotective drugs for glaucoma management such as small-molecule therapeutics, recombinant therapeutic proteins and small-molecule bioactive peptides. Particularly, small peptides, which show high target specificity, high potency and low toxicity compared with small molecules, possession of the advantages of low immunogenicity and high cost-effectiveness over recombinant therapeutics, may become most important choice for neuroprotection against glaucoma of next generation.