To reduce harvest losses of a pepper harvester with a drum of elastic tooth type picking mechanism, this paper proposes an optimization method using AHP (Analytic Hierarchy Process) and RSM (Response Surface Methodology), thereby identifying the optimal harvesting parameters. Based on Hertz’s contact theory and projectile motion theory, dynamic and kinematic models were established for the picking and casting stage. Key parameters influencing harvest loss were identified as drum rotational speed, operating speed, and tooth spacing. A simulation model was constructed, and solved within LS-DYNA of ANSYS Workbench. A Box–Behnken design in RSM was employed to investigate the effects of drum rotational speed, operating speed, and tooth spacing on the picking rate, breakage rate, and loss rate. The optimal parameters, obtained through RSM optimization after AHP weighting, were determined to be a drum rotational speed of 182 r/min, an operating speed of 0.42 m/s, and a tooth spacing of 40 mm. A test bench was designed for validation, with simulation results deviating from experimental results by less than 5%. With optimized parameters, the picking rate increases from 89.73% to 95.13%, the breakage rate decreases from 3.21% to 2.66%, and the loss rate decreases from 5.16% to 3.95%. This study provides a theoretical foundation and practical reference for optimizing the drum with elastic tooth type picking mechanism in pepper harvesters.