The "milky disease" of Chinese mitten crabs caused by Metschnikowia bicuspidata is the most serious disease of the cultivated Chinese mitten crabs in northern China, and there have been no control measures for this disease until now. In this study, a fungus 2JHP001 with a strong antagonistic effect against M. bicuspidata was screened from soil samples by the double-layer plate method and the punching method. The strain was identified as Aspergullus sclerotiorum by analyzing its morphological, molecular, physiological and biochemical characteristics. The UHPLC-MS analysis of the ethyl acetate extract showed that it contained maleic acid derivatives, terpenes, polyketides, 2,5-diketopiperazines, alkaloids, and other compounds. The morphology of yeast after treatment with 2JHP001 crude extract was observed by SEM and TEM, and the results showed that this treatment caused severe distortion of the yeast and different degrees of damage to the yeast cell walls, cell membranes and organelle. Moreover, animal experiment demonstrated that the survival rate of Chinese mitten crabs infected with "milky disease" was increased by 22.3 % within 21 d. The study provide new idea and possible strategy for the prevention and control strategy of "milky disease" in Chinese mitten crabs.