Abstract: Sulfonylureas (SUs) are valuable in the treatment of diabetes mellitus, when it is mixed with herb each can alter the others pharmacokinetics profile. The interaction can be beneficial or sometimes contraindicated. The study aimed to investigate the interaction of some dietary drinks with respect to their traditional uses, to that of the antidiabetic drug as glimepiride. Seventy adult male albino rats divided into main two groups, ten rats were considered as a negative control group (NCG) and the others were administered a single dose of Alloxan (120 mg/kg body weight) that induced with diabetes, then divided into the following groups, positive control group (PCG), glimepiride group (GG) were administered orally antidiabetic drug as glimepiride (4 mg/kg orally once daily). Another diabetic rats given each different drinks plus antidiabetic agent glimepiride, which administered orally (by stomach tube) for 30 days. Rats were divided according to the type of drink given into fourth subgroups, as follow: glimepiride plus 0.5 g fenugreek group (GFG1), glymepiride plus 1 gm fenugreek group (GFG2), glymepiride plus 0.5 gm coffee group (GCG3) and glymepiride plus 1 gm coffee group (GCG4). Serum total cholesterol, triglycerides, HDLc, VLDLc, LDLc, ALT, AST, ALP, urea, creatinine, albumin, glucose and insulin was estimated. The results illustrated that after 6 weeks of experimental duration, the mean comparable in both GG and GFG1 to NCG had insignificant change for FBG (98.33±2.52, 104.90±11.62 and 97.27±11.91, respectively), whereas for other treated groups had been a significant decline. While at long period, GFG2 had the best effect that did not differ significantly to another studied drink at different doses as compared to GG and GFG1. It was concluded that the inter- positive effect between antidiabetic glimepiride and fenugreek or coffee drink on glycemic profiles was stated.