The growing number of diabetes coupled with the harsh side effects of some synthetic drugs has led to the increasing search for alternative medicine which are relatively cheap with minimum side effects. Objective: To investigate the anti-diabetic effect of ethanolic extract of Carica papaya and Psidium guajava extracts separately and in combination, and the effect of treatment on hepato-renal performance. Methods: Papaya and guava leaves were macerated in 98% ethanol for extraction. Results: The result showed that ethanolic leaf extract of P. guajava and C. papaya significantly (P< 0.05) reduced blood glucose level, Total Cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and significant increase in high density lipoprotein (HDL) as compared to diabetic control group. Serum activities of liver enzymes such as aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) was slightly elevated that indicate hepatotoxic nature of plant extracts. The level of gamma-glutamyl transferase (GGT), bilirubin and HbA1C level were restored to normal range. A slight reduction in body weight (P>0.05) of treated groups was observed. Serum urea and creatinine concentration was restored to normal level in treated rats with regeneration of kidney function. Conclusions: The study concluded that individual and combined plant extract show anti-hyperglycemic effect but the combined remedy at this dose show hepatotoxicity.