Background and objective The plethora of anti-diabetic agents available today has many side effects, especially on chronic usage. Hence, alternative approaches utilizing natural and synthetic agents are sought after. Cumin has been shown to be beneficial in treating diabetes. This study evaluates the anti-diabetic effect of cumin and glyburide in the streptozotocin induced diabetes model in rats, and investigates their pharmacodynamic interactions and its implication in diabetes. Methodology The phytoconstituents present in the ethanolic cumin seed extract were determined using appropriate analytical methods. After acute toxicity studies (OECD 2001), the anti-diabetic effect of the extract was evaluated in wistar rats. The rats were divided into five groups - Groups I and II served as the normal and diabetic control. Group III was the standard control (glyburide 5 mg/kg), while groups IV and V received the extract (600 mg/kg) and a combination of the extract (600 mg/kg) and glyburide (2.5 mg/kg; half dose). Biochemical parameters viz. plasma glucose and glycosylated haemoglobin, were measured periodically during the 28 day treatment. On the 28th day, oral glucose tolerance test, lipid profile, renal profile and histopathological evaluation were performed after completion of the study. To investigate the nature of herb-drug interaction, HPLC analysis for estimation of glyburide concentration in the blood was conducted. Results Acute toxicity studies showed the extract to be safe till a dose of 2 g/kg. The extract alone, and in combination with glyburide (half-dose), significantly lowered elevated glucose (by more than 45% from baseline; without producing hypoglycemia), and other lipid and renal parameters. The effects produced by 2.5 mg/kg glyburide, and 5 mg/kg glyburide (without extract) were similar. Histopathological analysis also showed that the extract was able to reverse the degeneration brought about by streptozotocin which was especially notable on the pancreatic and renal tissue. HPLC analysis revealed differing pharmacokinetics of glyburide in the groups treated with 5 mg/kg dose, and 2.5 mg/kg + 600 mg/kg extract. Conclusion The results obtained in this study suggest that Cuminum cyminum L. is a promising anti-diabetic agent, and exhibits pharmacodynamic interaction with glyburide to mitigate symptoms of diabetes mellitus.