Lagerstroemia speciosa is a woody tree with numerous therapeutical properties that improve metabolic defects caused by elevated glucose and lipid levels. We have investigated the safety and efficacy potentials of L. speciosa leaf extract (LSLE) by conducting toxicity studies comprising acute short-term studies of 28 days and long-term studies of 90 days duration in rodent models of both sexes. The acute toxicity studies revealed that the LD50 value exceeded 3000 mg/kg of body weight. For the sub-chronic toxicity assessment, Wistar rats were administered LSLE concentrations orally every day for 28 days, with a control group receiving 0.5% Tween 80. A notable reduction in body weight gain, food intake, glucose and pancreatic amylase levels was recorded in the LSLE-treated group. These crucial findings were validated in a chronic toxicity study involving Wistar rats, which were orally administered LSLE daily for 90 days. The percentage of food intake was observed to decrease progressively. Nevertheless, no remarkable alterations were noted in the hematological parameters, histological analyses, relative organ weights, or other biochemical parameters, except for glucose and pancreatic amylase. The overall findings indicate that long-term administration of LSLE is non-toxic and very effective in maintaining the percentage of body weight gain through multiple mechanisms.