We have synthesized new melatonin analogs 4,6,11,12 based on 3-hydroxy-2-oxindoles (11) and hydroxy-free 2-oxindoles (4,6,12) and evaluated their neuroprotective and antioxidant properties as well as their ability to reduce intraocular pressure. Reductive amination was used to obtain new 5-(benzylamino)-substituted (indolin-3-yl)acetonitriles 11 and (indolin-3-yl)acetic acids 12 with high yields. Compounds 4a,c, 6a and 11a,d,h,j-l demonstrated IOP reduction effect in range 15-27% similar to the effect of reference compounds melatonin and timolol (12% and 18%, respectively). 5-(Benzylamino)-substituted 3-hydroxy-2-oxindoles 11, unlike compounds 4,6, inhibited lipid peroxidation in range 2.075-13.012 µM. Inhibition of NQO2 associated with antioxidant properties of melatonin was also evaluated for synthesized compounds and it was found that compound 11h showed the best NQO2 inhibitory activity with an IC50 = 39 μM (vs. melatonin IC50 = 64 μM). All synthesized compounds 4,6,11,12 at a concentration of 30 µM do not possess the mitochondrial toxicity. Moreover, no disruption of tubulin polymerization was observed even in the presence of 100 μM of the compounds. Thus, 3-hydroxy-2-oxindole derivatives 11 can be used for drug design of first-in-class antiglaucoma drugs with antioxidant and neuroprotective properties.