The aim of this study was to compare the mechanism of action of Bridelia ferruginea root bark hydro alcoholic extract to metformin and glibenclamide on diabetes and evaluate its safety in vitro. Materials and Methods: A single dose of B. ferruginea extract (250 mg/kg), metformin (100 mg) and glibenclamide (5 mg/kg) was administered to normal blood glucose level Wistar rats. Blood glucose and insulin were measured 3 hours after administration of substances. Another daily administration of substances at the same doses for 14 consecutive days was performed, blood glucose and insulin level were determined at 0, 7, 14th day. MTT and red neutral assay were performed in Vero and N2A cells for in vitro toxicological evaluation. In a single administration, we noticed that B. ferruginea and metformin have no significant effect on insulin secretion nor on basal blood glucose level during the 3 hours compared to rats that received distilled water. Glibenclamide significantly (P< 0.001) reduced blood glucose level to the third time with an increase in insulin concentration. In repeated dose, we also note that B. ferruginea and metformin had no effect on insulin secretion nor on basal blood glucose during the 14 days of treatment. We note a significant increase in insulin levels and reduction of blood glucose level in animals that received glibenclamide. For MTT assay, the IC50 was 245 µg/mL for N2A cell and 286 µg/mL for Vero cell. With the neutral red assay, IC50 was 211 µg/mL for N2A cells and 317 µg/mL for Vero cells. These results show that Bridelia ferruginea root bark hydro alcoholic extract would have a similar mechanism of action to that of metformin.