In this paper, the metabolic regulation model of the body during weight loss is established according to the numerical variation law of the three major nutrients and the biological principles. The changing trend of the solution of the model is qualitatively analyzed by using the theory of time-varying differential equation. According to the normal values of the three major nutrients and the ketone body, the sufficient conditions for safe weight loss under the three ways of weight loss during dieting, exercise and drug are provided respectively. Combining with the actual data, the model parameters are identified by the numerical analysis method. The feasible range and simulation curve of the three major nutrients and the ketone body under three weight loss modes are given as well. Finally, the unsafe factors in the process of weight loss are analyzed, and the weight loss suggestions beneficial to health are given.