Saponins (Sap) are effective bioactive compounds for ameliorating various diseases complications. This study addressed the effects of co-treatment with Sap and metformin (Met) on the biochemical status of type 2 diabetes mellitus (T2-DM) rats. Forty male Sprague-Dawley rats were divided into 5 groups (n = 8) as follows: group 1 (Gp1) was the negative control group. Gp2 was fed on a high fat diet (HFD) for 8 weeks (wks) and received a single intraperitoneal (i.p) injection of 30 mg/kg streptozotocin (STZ) after 8 wks to induce T2-DM. Gp3 was treated as Gp2, after 8 wks rats received 250 mg/kg Met by oral gavage daily for 4 weeks. Gp4 was treated as Gp2, and after 8 wks rats received 300 mg/kg Sap by oral gavage daily for 4 weeks. Gp5 was treated as Gp2, after the 8 wks rats received it, and then co-treated with Met as in Gp3 and Sap as in Gp4. The percentage of body weight (% b.wt) changes, hematological, and biochemical parameters were determined. The results showed that co-treatment with Met and Sap led to significant improvement in the % b.wt of T2-DM rats. Co-treatment of T2-DM rats with Met and Sap led to synergistic effects in the reduction of serum glucose levels and an increase in the C-peptide levels. Co-treatment of T2-DM rats with Met and Sap led to significant improvements in the hepato-renal functions and antioxidant status. Sap could play an important role in regulating T2-DM and can be developed as a promising natural material for diabetes management.