The echo signal of ultrasonic flowmeter usually has noise interference, which makes it difficult to locate the echo signal accurately. In order to filter out the noise in the ultrasonic echo signal, a signal denoising method based on the optimized variational modal decomposition (VMD) algorithm is proposed. Firstly, the information entropy of the mutual information criterion is used to associate the genetic algorithm with VMD. Then, the sample entropy is used as the fitness function to adaptively optimize the parameter combination in VMD algorithm. Finally, the original signal is decomposed, the effective signal is calculated through the correlation coefficient, and the effective signal is reconstructed after further denoising. The simulation results show that the proposed method can effectively filter out the noise in ultrasonic echo signal and retain the useful signal completely.