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Aiming at the problem of mixture separation with significant differences in various shapes after the Potosia brevitarsis larva biotransformation the residual film mixture to meet the premise of biological activity, a segmented drum type pneumatically assisted Potosia brevitarsis larva biotransformation mixture separation device was designed. Through physical experiments and theoretical calculations, the resistance coefficient partitions and theoretical suspension speeds of Potosia brevitarsis larva, frass, and residual films were determined. Its accuracy was verified by using a suspension speed bench test, which can provide data basis for subsequent fluid-structure interaction simulations. Through theoretical analysis and EDEM-Fluent coupling method, the screening process of residual film, larvae and frass was simulated, and the main structural parameters and working parameters of the device were determined. The rotation speed of the drum screen, the inclination angle of the drum screen and the fan wind speed were selected as test factors. The residual film impurity content rate and the frass film content rate were tested as test indicators. A single factor test was conducted to determine the reasonable range of the levels of each factor. Based on the results of the single factor test, a three-factor and three-level quadratic regression response surface test was designed and a regression model was established. The test results showed that the order of factors affecting the impurity content of the residual film was fan speed, drum screen inclination angle, and drum screen speed. The order of factors affecting the film content of frass was drum screen rotation speed, drum screen inclination angle, and fan wind speed. After optimization, the optimal working parameter combination was drum screen rotation speed of 21.79r/min, drum screen inclination angle of 3.58°, and fan wind speed of 5.52m/s. The material screening test was carried out with this parameter combination, and the average impurity content rate of the residual film and the film content rate of the frass were 8.96% and 1.52%, respectively. The relative errors with the theoretical optimization values were less than 5%. The research can provide a reference for the design of separation devices for mixtures containing biological activity and significant differences in shape.