The present study designed to evaluate the toxicity of Cerastes cerastes (Cc) venom on male albino rats and the possible ameliorative role of Alkanna orientalis (Ao) extract against venom toxicity. Forty-eight adult male albino rats (180 ± 200 g) divided into 6 groups. Group I injected intraperitonial with physiological saline (100μl). Group II injected intraperitonial with Ao extract (250 mg/kg/BW). Group III was injected with 1/10 LD50 of Cc venom (0.435 mg/kg/BW). Group IV injected intraperitonial with Cc venom (0.435 mg/kg/BW) then immediately injected with Ao extract (250 mg/kg/BW). Group V was given Ao extract orally (250 mg/kg/b.wt) then after 2 hours injected with Cc venom (0.435 mg/kg/BW) Group VI was injected with Cc venom (0.435 mg/kg/BW) then was injected immediately with immunoglobulin (300μl). Group III showed a significant increase in serum creatinin, urea, uric acid as well as a significant decrease in serum total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, glucose level, calcium and cholinesterase when compared with control group. As well as, Ao extract when given intraperitonial immediately or orally 2 hours before Cc venom as antidote, it minimizes the changes of previous biochemical parameters. groups IV and V when compared with group VI, it showed that Ao extract considered more effective antidote than antivenom immunoglobulin for Cc venom renal, lipogram and cholinergic toxicity. In conclusion, Ao extract showed a new therapeutic and prophylaxis agents against Cc venom renal, lipogram and cholinergic toxicity.