AbstractObjectives:To evaluate the preventive effects of Korean red ginseng (KRG) on gentamicin (GM)‐induced ototoxicity and to identify the effective components of KRG.Study Design:In vivo and in vitro studies.Methods:Thirty‐five Sprague‐Dawley rats were divided into four groups. The GM group (n = 15) received intraperitoneal injections (IPI) of GM (160 mg/kg) for 5 days. The KRG + GM group (n = 12) was treated with intragastric feeding of KRG (500 mg/kg) for 12 days with 5 days of IPIs of GM. KRG (n = 4) and control (n = 4) groups were treated with KRG and saline, respectively. Auditory brainstem response (16 or 32 kHz) and Rotarod treadmill tests were done before and after treatments. Cochleas were evaluated by a scanning electron microscope (SEM) and phalloidin staining. Ginsenosides Rb1, Rb2, Rg1, and Re were evaluated as the water‐soluble terazolium salt assay, annexin V/propidium iodide assay, and Western blots in HEI‐OC1 cells.Results:Posttreatment hearing thresholds in GM, KRG + GM, KRG, and control groups were: 27.7 ± 7.2 dB, 23.1 ± 4.1 dB, 16.9 ± 2.6 dB, and 21.3 ± 3.5 dB, respectively, for 16 kHz, 30.5 ± 6.6 dB, 25.2 ± 4.3 dB, 22.5 ± 2.7 dB, and 22.5 ± 3.8 dB, respectively for 32 kHz. The KRG + GM group had significantly better hearing than the GM group (P < .05). On SEM and phalloidin staining, the GM group showed severe loss of stereocilia in the basal outer hair cells and a few losses in the middle turns, whereas the KRG + GM group showed relatively intact hair cells. Balance impairment in treadmill tests was not definite in any group. Rb1 and Rb2 showed more effective protection than other components.Conclusions:KRG protects against GM‐induced hearing loss and hair cell death in rats. Laryngoscope, 2011