There is a rise in the use of Celosia isertii and Costus lucanusianus in the treatment of many ailments and diseases around Nigeria and Africa either by oral consumption or by consuming it in liquid form. However, the safety of these plants is not known and has not been established. Despite claimed success in treating diseases, it is imperative that a safety evaluation of the plants are carried out. This study was aimed at evaluating the safety of the aqueous and ethanolic extracts of Celosia isertii and Costus lucanusianus on the liver and renal function in Wistar rats administered varying doses of the extracts of Celosia isertii and Costus lucanusianus. Sixty five (65) adult Wistar rats, weighing between 120-130kg were randomly divided into thirteen (13) groups with n=5 rats per group. Twelve (12) groups were treated with varying doses (250, 500, 1000 mg/kg/d) of either aqueous or ethanolic extract of each plant as single daily dose for twenty-eight (28) days using oral canula. The remaining one (1) group was treated with potable water in lieu of extract. The animals were euthanized under chloroform anaesthesia and certain organs (liver and kidneys) were excised. Serum homogenates were used for enzyme (aspartate aminotransferase, AST, alanine aminotransferase, ALT and alkaline phosphatase, ALP) as well as to determine the concentrations of urea, and creatinine of the animals. Results show AST/ALT ratio to be approximately 2; with a significant (p< 0.05) decrease in the activity of liver enzymes of the treated groups in a dose dependent manner when compared to the control However, no significant (p> 0.05) changes in the concentration of serum urea and creatinine of the treated groups compared to the control of the animals. A high AST/ALT ratio suggest impaired liver function, however, the liver is not the only site of AST or ALT synthesis. As a result of the lower values of AST, ALT and ALP obtained from treatment groups as compare to the control as well as the insignificant (p>0.05) changes in levels of urea and creatinine in serum of both control and experimental rats, Costus lucanusianus and Celosia isertii extracts could be safe at the doses mentioned as they did not show marked toxic effects on the liver enzymes and some selected kidney markers. Hence, they are likely to be beneficial in treating diseases without affecting the integrity of the liver and kidney.