In present study, we investigated hypoglycemic and antihyperglycemic potential of five extracts (water, ethanol, methanol, hexane, and chloroform) of four plants (i.e., seeds of Eugenia jambolana, fruits of Momordica charantia, leaves of Gymnema sylvestre, and seeds of Trigonella foenum graecum) alone and/or in combination with glimepiride in rats. Ethanol extract of E. jambolana, water extract of M. charantia, ethanol extract of G. sylvestre, and water extract of T. graecum exhibited highest hypoglycemic and antihyperglycemic activity (most active) in rats among all the extracts, while hexane extracts exhibited least activities. Most active extracts were further studied to dose-dependent (200, 100, and 50 mg/kg body weight (bw)) hypoglycemic and antihyperglycemic effects alone and in combination with glimepiride (20, 10, and 5 mg/kg bw). The combination of most active extracts (200 mg/kg bw) and lower dose of glimepiride (5 mg/kg bw) showed safer and potent hypoglycemic as well as antihyperglycemic activities without creating severe hypoglycemia in normal rats, while higher doses (200 mg/kg bw of most active extracts, and 10 and 20 mg/kg bw of glimepiride) were generated lethal hypoglycemia in normal rats. From this study, it may be concluded that the ethanol extract of E. jambolana seeds, water extract of M. charantia fruits, ethanol extract of G. sylvestre leaves, and water extract of T. graecum seeds have higher hypoglycemic and antihyperglycemic potential and may use as complementary medicine to treat the diabetic population by significantly reducing dose of standard drugs.