Puerariae Lobatae Radix (PLR) is the dried root of the leguminous plant Pueraria lobata and is a common component of health products and medicines. Although it is considered safe, some studies have reported that PLR has hepatotoxicity and estrogen‐like effects. In this study, the safety of high doses of PLR water extract administered to adolescent SD rats for 30 days was evaluated by biochemical, histopathological, and metabolomic analyses. Overall, there were no significant differences between the low‐dose and blank control groups in parameter values, including organ wet weight, organ coefficient, routine blood indicators, serum biochemical indexes of liver and renal function, levels of estradiol and testosterone, histopathological parameters, and primary differential metabolite profiles. Compared with the blank control group, the high‐dose group may have a certain effect on the liver. These effects might be mediated by abnormal phenylalanine, tyrosine, and tryptophan biosynthesis or phenylalanine metabolism. However, histopathological analyses did not show differences in the liver, kidney, breast, uterus, ovary, testis, and epididymis between the control group and the group treated with a high dose of PLR water extract. PLR water extract did not significantly promote the precocity of male and female sexual organs. Overall, PLR water extract is relatively safe for adolescent SD rats.