One of the strategies proposed for combating advanced glycation end‐products (AGEs) and its devastating effects is the breaking of preformed AGEs‐protein cross‐links. AGEs are linked to the pathogenesis of late onset complications of diabetes mellitus, age‐related and neurodegenerative diseases.This study evaluated the AGEs‐protein cross‐link breaking effect of some medicinal plants used for managing diabetes mellitus. These plants, selected based on their blood glucose lowering property, include Sclerocarya birrea, Psidium guajava, Murraya koenigiiand Cinnamon cassia.Of the selected plants, the highest AGEs‐protein cross‐link breaking effect was observed with the hexane and ethyl acetate leaf extracts of Psidium guajava.Methanol extracts of both Psidium guajava leaf and Sclerocarya birrea stem‐bark also showed high cross‐link breaking effect. Chemical screening tests for the presence of phytochemicals and Gas Chromatography Mass Spectrometry (GC‐MS) analysis for the detection and identification of the phytoconstituents in the extracts were also carried out.Compounds detected in the hexane leaf extract of Psidium guajava, using GC‐MS, include I‐(+)‐Ascorbic acid 2,6‐dihexadecanoate, Octadecanoic acid (Stearic acid), Vitamin E (D‐alpha‐tocopherol), Alpha‐Tocopherol‐beta‐D‐mannoside and 2,6,10,14,18,22‐Tetracosahexaene, 2,6,10,15,19,23‐hexamethyl‐, (all‐E) (Squalene). The hexane leaf extract of Psidium guajava was subjected to column chromatography. Using Nuclear Magnetic Resonance and Infra‐red spectroscopy, the isolated compound from the hexane leaf extract of Psidium guajava was identified as a flavonoid.The results of the study indicate that present in these extracts are potent agents with the ability to break AGEs‐protein cross‐links which could be exploited for drug discovery.