Introduction: Medicinal plants such as Cnidoscolus aconitifolius (CA) have been studied over the years for their protective and curative potentials against a myriad of common global health challenges such as hepatorenal injuries. Objectives: To ascertaining the effects of the hydromethanol leaf extract of CA (HMLECA) on hepato-renal parameters in adult male wistar rats. Method: A total of 18 adult male wistar rats were divided into 3 groups of six rats each. Group I served as the negative control which received distilled water while groups 2 and 3 served as extract treatment groups which received 200 and 400 mg/kg BW of the HMLECA respectively. The administration was daily for a period of 58 days while blood sample for the biochemical analysis was drawn via cardiac puncture at the end of the study following light chloroform anaesthesia. Results and Discussion: The results showed that the administration of both doses of the extract produced no significant (P<0.05) effect on the levels of serum liver enzyme (AST, ALT, ALP), TP, ALB, electrolytes (K+, Na+ and HCO3–), Creatinine and Urea while that of the 400 mg/kg BW produced significant (P<0.05) decrease in the level of TB and Cl –. Hence, the administration of the leaf extract in this study did not elicit any toxic effect on both the liver and kidney functions and could be effective as hepato-renal protective agent. Keywords: Cnidoscolus aconitifolius, Liver function, Liver enzymes, Renal function, Serum biochemicals, Serum electrolytes