Background <p>Gabapentin is the pharmacologic treatment of choice for symptom relief in diabetic neuropathy. However, its effect on high glucose (HG)-induced neurotoxicity and genotoxicity under diabetic neuropathy conditions remains unclear. The aim of this study was to investigate the effects of gabapentin on cytogenotoxicity in HG-induced neuropathy in dorsal root ganglion (DRG) neurons.</p> Methods <p>DRG neurons were isolated from neonatal Sprague-Dawley rats (<i>n</i> = 10). After treatment of these neurons with HG (45 mmol/L) and gabapentin (1,10, 100, and 1000 µM), cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2&#xa0;H-tetrazolium bromide (MTT) assay. Furthermore, the effects on DNA damage in DRG neurons exposed to HG (45 mmol/L) and gabapentin (10 and 100 µM) were investigated by comet assay.</p> Results <p>When HG + Gabapentin (1 µM), HG + Gabapentin (10 µM), HG + Gabapentin (100 µM), and HG + Gabapentin (1000 µM) groups were compared with the HG group, no statistically significant change in cell viability was determined (<i>p</i> &gt; 0.05). HG + Gabapentin (10 µM) and HG + Gabapentin (100 µM) groups were not statistically significant in genotoxicity compared to HG group (<i>p</i> &gt; 0.05).</p> Conclusions <p>Our results suggest that gabapentin does not modulate HG-induced cytogenotoxicity in HG-exposed DRG neurons. Our findings, which emphasize the safety of gabapentin in diabetic neuropathy, need more detailed studies.</p> Clinical trial number <p>Not applicable.</p> Graphical Abstract <p>Gabapentin did not alter cytotoxicity in HG-exposed DRG neurons, an in vitro model of diabetic neuropathy. Gabapentin showed cytotoxic effect at high doses in healthy DRG neurons and high affinity for the antiapoptotoic protein BCL-2 in a molecular docking study. Gabapentin neither modulated HG-induced genotoxicity in DRG neurons nor showed high affinity for DNA in silico.</p> <p></p>