In Nigeria, rural inhabitants often resort to herbal remedies and dietary control for the treatment and management of various forms of diabetes mellitus. This study was conducted to provide the rationale for the use of Psidium guajava leaves as a potent traditional anti-diabetic remedy. The crude leaf extracts of n-hexane, methanol, and ethyl acetate of Psidium guajava were separately prepared by cold maceration. Then, ethyl acetate crude extract of Psidium guajava leaves was fractionated by column chromatography to yield ethyl acetate bulked fractions: EF-I (1-75), EF-II (76-150), and EF-III (151-250). The n-hexane, ethyl acetate, and methanol crude leaf extracts and ethyl acetate bulked fractions (EF-I, EF-II and EF-III) were evaluated for anti-diabetic activity in alloxan-induced diabetic mice. The blood sugar levels of treated and untreated alloxan-induced diabetic mice were assayed as indices of anti-diabetic effect. The phytochemical constituents of both crude extracts and ethyl acetate fractions of Psidium guajava leaves and the mean lethal dose (LD50) of ethyl acetate crude leaf extract of Psidium guajava were determined. The mean lethal dose (LD50) of ethyl acetate crude leaf extract was calculated to be 1500mg/kg b.w. The results indicated that oral administration of ethyl acetate, n-hexane, methanol crude extracts, and ethyl acetate bulked fractions of Psidium guajava leaves at a dose of 100mg/kg b.w on treated groups exhibited much significant[pHC>MC>EF-I>EF-II>EF-III. The results of phytochemical screening of the crude extracts and ethyl acetate bulked fractions showed the presence of tannins, flavonoids, saponins, alkaloids, terpenoids, glycosides, and steroids while reducing sugar was absent. The results from this study gives credence to the use of Psidium guajava as an anti-diabetic agent in the management of diabetes mellitus.