The aim of our study was to investigate the potential effects of alpha-lipoic acid (ALA) and resatorvid (RES) on gentamicin-induced hepatotoxicity. Thirty-four rats were divided into the following groups: Healthy control (n=6), Gentamicin (GNT, 80 mg/kg, n=7), GNT + Sham (10% hydroalcoholic solution, n=7), GNT + RES (5 mg/kg, n=7), and GNT + ALA (100 mg/kg, n=7). In the GNT group, a statistically significant increase in ALT levels and a significant decrease in total protein (TP) and albumin (TA) levels were observed compared to the control group. On the other hand, a significant increase in NRF-2, NF-κB, NR4A2 and CAS-3 expression was detected in the GNT group as compared to the control group. Simultaneous administration of RES or ALA with GNT led to a significant decrease in ALT levels compared to the GNT group. In addition, these treatments caused a significant increase in TP and TA levels. RES administration caused a significant decrease in gene expression compared to the GNT group. On the other hand, simultaneous ALA treatment with GNT caused a significant decrease in NRF-2, CAS-3 and NF-κB expression and partially reduced NR4A2 expression. These findings draw attention to the potential of RES or ALA to alleviate gentamicin-induced hepatotoxicity and to their increased efficacy in the treatment of infections.