Diabetes mellitus (DM) is a metabolic syndrome that is currently being managed using different brands of prescribed medications; however, these medications are associated with different side effects. As such, medical plants are considered an alternative in traditional medicines for treating DM as they have no side effects. The present study was conceived with the aim of studying generally medicinal plants extracts in terms of their a-amylase and a-glucosidase inhibitory activities; to study the renal, hepatic, and pancreatic protective effects of these EIE: OsC (2:1) and ElE:PgC (2:1) plant extracts on streptozotocin (STZ)-induced diabetic rats after 30 days of treatment. Sprague-Dawley rats were intraperitoneally injected with STZ (60 mg/kg) to induce DM. The rats were randomly grouped into 7 groups of 5 rats each based on the intended treatment for the groups; the seven groups of rats are as follows: NC = normal control rats; NEIE:PgC (2:1) normal rats treated with combined E. longifolia and P. granatum extracts at a combination ratio of 2:1 (200 mg/kg); NEIE:OsC (2:1) = normal rats treated with combined extracts of E. longifolia and O. stamineus at 2:1 combination ratio; DC = diabetic control rats; DG = glibenclamide (0.6 mg/kg)-treated diabetic rats; DEIE:PgC (2:1) diabetic rats treated with combined extracts of E. longifolia and P. granatum at a ratio of 2:1 (200 mg/kg); DEIE: OsC (2:1) = diabetic rats treated with combined extracts of E. longifolia and O. stamineus at the same ratio. All the animal groups were treated for 4 weeks and after the treatment period, the blood glucose level, body weight, liver and renal functions, and histopathological changes of the endocrine pancreas, liver and kidneys were examined in all the experimental rats. The extracts with ≥ 50% enzyme inhibition activity were reported in A. bilimbi, A. paniculata, O. stamineus, E. longifolia and P. granatum. The outcome of the study showed that a 2:1 combination of ethanolic extract of E. longifolia and chloroform extract of P. granatum showed gave the maximum rate of a-glucosidase inhibition (148.06%), while a similar combination of ethanol extract of E. longifolia and chloroform extract of O. stamineus offered the greatest a-glucosidase inhibition (137.43%). GC-MS-based phytochemical analysis of the extracts showed the presence of fatty acids in the extracts, with palmitic acid being the highest occurring fatty acid in the extracts of O. stamineus. Results showed a significantly increase (p<0.05) in fasting blood glucose level, body weight, AST, ALT, ALP and GGT levels, total protein, albumin, globulin, blood urea level and serum creatinine level in the DC group compared to the NC group. However, changes in these parameters were ameliorated in the DEIE: OSC (2:1), DEIE:PgC (2:1) and DG groups; the ameliorative effect was significant in the DG and DEIE:PgC (2:1) groups only (p<0.05). Examination of the liver sections showed mild vacuolation in the cytoplasm of the hepatocytes, congestion in the central vein, portal vein and sinusoid, as well as mild hepatic cord disarrangement in the DC group. These pathological changes were ameliorated in the ElE:OsC (2:1), EIE:PgC (2:1) and glibenclamide-treated rats. Histological observation of the pancreas sections of the rats in the DC group showed scanty number of small sized islets of Langerhans which were scattered within the acini. The islets cells have pyknotic nuclei and scanty eosinophilic cytoplasm. Fibrosis was noted in some areas while sections of the kidneys showed normal histological structure (glomeruli, renal tubules, blood vessels and interstitium) of the kidneys the NC, DM, and treated rats. In conclusion, the outcome of this study showed that ElE:OsC (2:1) and EIE:PgC (2:1) plant extracts could serve as potential alternatives for the treatment and control of diabetes mellitus and its related complications in diabetes mellitus rats.