The use of gentamicin (GM) is limited due to its nephrotoxicity mediated by oxidative stress. This study aimed to evaluate the capacity of a flavonoid-rich extract of L. elderflower (SN) to inhibit lipoperoxidation in GM-induced nephrotoxicity. The HPLC analysis of the SN extract recorded high contents of rutin (463.2 ± 0.0 mg mL), epicatechin (9.0 ± 1.1 µg mL), and ferulic (1.5 ± 0.3 µg mL) and caffeic acid (3.6 ± 0.1 µg mL). Thirty-two Wistar male rats were randomized into four groups: a control group (C) (no treatment), GM group (100 mg kg bw day GM), GM+SN group (100 mg kg bw day GM and 1 mL SN extract day), and SN group (1 mL SN extract day). Lipid peroxidation, evaluated by malondialdehyde (MDA), and antioxidant enzymes activity-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX)-were recorded in renal tissue after ten days of experimental treatment. The MDA level was significantly higher in the GM group compared to the control group ( < 0.0001), and was significantly reduced by SN in the GM+SN group compared to the GM group ( = 0.021). SN extract failed to improve SOD, CAT, and GPX activity in the GM+SN group compared to the GM group ( > 0.05), and its action was most probably due to the ability of flavonoids (rutin, epicatechin) and ferulic and caffeic acids to inhibit synthesis and neutralize reactive species, to reduce the redox-active iron pool, and to inhibit lipid peroxidation. In this study, we propose an innovative method for counteracting GM nephrotoxicity with a high efficiency and low cost, but with the disadvantage of the multifactorial environmental variability of the content of SN extracts.