<p>Gabapentin (GBN) is an anti-seizure medication that is also used to treat nerve pain and other diseases. However, its misuse is currently a growing worry, as it may pose a significant health danger. The present study aimed to evaluate the protective effect of melatonin (MEL) and bee pollen (BP) as antioxidants against GBN-induced hematotoxicity and hepatorenal toxicity in female Albino rats. In this study, fifty-six adult female albino rats were divided into seven groups (<i>n</i> = 8 each), served as control, GBN, MEL, BP, MEL + GBN, BP + GBN, and MEL + BP + GBN treated groups. Results showed that oral administration of GBN resulted in a hematological toxicity as confirmed by a significant reduction in RBCs, Hb concentration, Ht%, MCV, MCH, platelets as well as altering of leukocyte profiles, WBCs, neutrophils, lymphocytes, monocytes, eosinophils and basophils. The biochemical results of liver and kidney functions showed a significant decrease in serum glucose, total protein, triglycerides, urea and uric acid. However, a significant increase in albumin, cholesterol, creatinine as well as ALP, AST, and ALT liver enzymes compared to the control was found. The oral administration of MEL and BP 12 h before GBN mostly ameliorates the altered hematological and biochemical parameters as well as hepatic and renal histopathological architecture to normal levels. In conclusion, Pre-treatment with MEL and BP, individually or together provided protection against the GBN induced changes in the blood parameters as well as hepatorenal structure and function.</p>