The invention discloses an efficient preparation method of low-value fish immunomdodulating peptides, relates to the development and utilization of low-value fish bioactive peptides and related anti-inflammatory drug products, and belongs to the technical field of low-value fish processing; the preparation method comprises the steps of preparing nemipterus virgatus myosin by a salt extraction method, fully expanding a high-spiral structural domain of myofibrillar protein by using a high-pressure homogenization method; fine-tuning a protein solution to pH 7.5, adding trypsin, performing enzymatic hydrolysis for 90 minutes, promoting an ultrafiltration membrane to separate a nemipterus virgatus protein enzymatic hydrolysate by using impressed current, and obtain a peptide fragment of 500 to3000 components; finally obtaining a powdery product by a freeze-drying method; the method can improve the degree of hydrolysis of the nemipterus virgatus myosin peptide, and the biological propertiesand yield of the immunomodulating peptides; the anti-inflammatory activity of the immunomodulatory peptides prepared by the method is better; the invention realizes the deep processing and comprehensive utilization of the low-value fish, and has important meaning for improving the added value of the low-value fish.