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Glaucoma is a neurodegenerative disease, our study aimed to evaluate the potential effects of Palmitoylethanolamide (PEA) supplementation on RGCs function by PERG examination, and to record effects on intraocular pressure, visual field and quality of life. It was a single centre, randomized, prospective, single blind, two treatment, two period crossover study on stable glaucoma patients on topical monotherapy comparing current topical therapy alone or additioned with PEA 600 mg one tablet a day. At baseline, at 4 and at 8 months, all patients underwent to complete ophthalmic examination, pattern electroretinogram, visual field, and quality of life evaluation. 40 patients completed the study: mean age 66.6 ± 7.6 years; 21 (52.5%) male; 35 POAG (87.5%). At baseline, most patients had an early visual field defect, the IOP was well controlled. At the end of the PEA 600 mg supplementation, a significantly higher (mean 0.56 μV, 95% CI 0.30-0.73, p < 0.001) in the P50-wave amplitude was observed; in the PEA period a significantly lower IOP (- 1.6 mmHg, 95% CI - 2 to 1.2, p < 0.001) and higher quality of life scores (+ 6.7, 95% CI 4-9.9, p < 0.001) were observed. Our study is the first to show promising effects of PEA on PERG and on quality of life in glaucoma patients.