This research aimed to evaluate the role of Glycyrrhiza glabra (GGE) and Saussurea costus (Costus) extracts in alleviating arsenic (As2O3)-evoked nephrotoxicity in chickens. Seven groups (36 chicks/group) were treated daily for 42 days as follows: control group; GGE group, obtained GGE (500 mg/kg feed); Costus group was given Costus orally (300 mg/kg bodyweight); As group, received As2O3 (30 mg/kg diet); As + GGE; As + Costus; As + GGE + Costus. The administration of GGE and/or Costus in As-intoxicated birds significantly decreased (p < 0.001) creatinine level relative to As group. Additionally, both extracts markedly reduced (p < 0.001) the renal malondialdehyde content and enhanced the antioxidant enzymes performance, which function via Nrf2/HO-1 signaling. Moreover, They downregulated the renal inflammatory cascade by suppressing the expression of TNF-α and NF-κB genes compared to As group. Furthermore, a significant decline in the levels of HSPs mRNA was recorded following treatment with GGE and/or Costus. Conclusively, GGE and Costus can be accounted as prospective antidotes in controlling As poisoning.