Obesity is of public concern worldwide, and it increases the probability of developing a number of comorbid diseases, including NAFLD. Recent research on obesity drugs and health demands have shown the potential of natural plant extracts for preventing and treating obesity and their lack of toxicity and treatment-related side effects. We have demonstrated that tuberostemonine (TS), an alkaloid extracted from the traditional Chinese medicine Stemona tuberosa Lour can inhibit intracellular fat deposition, reduce oxidative stress, increase cellular adenosine triphosphate (ATP), and increase mitochondrial membrane potential. It effectively reduced weight gain and fat accumulation caused by a high-fat diet, and regulated liver function and blood lipid levels. Moreover, it regulate glucose metabolism and improved energy metabolism in mice. TS also decreased high-fat diet-induced obesity and improved lipid and glucose metabolism disorders in mice, with no significant side effects. In conclusion, TS was shown to be a safe alternative for obese patients and might be developed as an antiobesity and anti-nonalcoholic fatty liver drug. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved.