This study aimed to determine the potential of quercetin and Zingiber officinale (ZO) Roscoe extract to alleviate the renal damage induced by dimethoate (DM) and fluoride (F^-) alone and by their combined exposure in rats. A total of 54 adult Wistar rats were randomly allocated to nine groups (n = 6). A sub-lethal dose of DM (1/10th of the median lethal dose) was administered by oral gavage alone and along with F^- (4.5 ppm, three-fold the permissible limit) in their drinking water continuously for 28 days. Chromatographical analysis revealed the presence of quercetin, curcumin, and other phytochemicals with strong antioxidant properties in ZO-rhizome extract. Severe changes were observed in the levels of the renal biomarkers and histoarchitecture after co-administration of the toxicants, indicating greater kidney damage. The administration of ZO extract (300 mg/kg) along with either or both toxicants led to a significant restoration of the biochemical markers and renal antioxidant profile and histology.