The present study was carried out to examine the protective effect of Zingiber officinale against the possible harmful effects induced by the α2-δ ligand, pregabalin, a novel antiepileptic drug with demonstrated efficacy. The results of this study put on show that the highest DNA damage (tail length, tail DNA % and tail moment) was in the group which received pregabalin only. The serum activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT) and gamaglutamyl transferase (γ-GT) were significantly increased in pregabalin treated group whereas, a significant decrease in serum total proteins was observed. The obtained results showed a significant decrease in both superoxide dismutase (SOD) and catalase (CAT) activities in pregabalin administered group. Zingiber officinale (Ginger) administration before pregabalin for two weeks then its co-administration with pregabalin concurrently till the end of the experiment (90 days), showed lower DNA damage (tail length, tail DNA % and tail moment), with a significant improvement in serum ALP, ALT and γ-GT besides clinical improvements in serum total proteins levels. Antioxidant enzymes SOD and CAT values showed significant increase. From the obtained results, it could be concluded that pregabalin in a dose of 20mg/kg body weight does has an oxidative DNA damage, elevating some serum biochemical parameters related to liver and produce an oxidative stress. The pretreatment with ginger two weeks before the co-administration of both drugs significantly minimize those harmful effects and considered to be a valuable aid in minimizing the hazards of pregabalin.