The invention provides a disease comprehensive prevention and control method for greenhouse-cultured penaeus vannamei. The disease comprehensive prevention and control method for the greenhouse-cultured penaeus vannamei is characterized by comprising the following steps: 1, water body regulation and control: (1), matching one culture pond with one disinfection tank, and disinfecting culture water by a bleaching powder, wherein the disinfected culture water can be used after three days; (2), properly irrigating the culture water to the culture pond before putting young shrimps, splashing bacillus preparations and effective microorganisms (EMs) over the whole culture pond, and putting the young shrimps into the culture pond after three days, wherein the bacillus preparations are activated by brown sugar, and the EMs are subjected to fermentation culture by utilizing aerated water of the disinfection tank; (3), no needing of discharging wastewater within 20-40 days before culturing, only adding water once at every three days, and adding the bacillus preparations and the seawater-cultured EMs at every six days; (4) starting discharging a small amount of wastewater once at the morning and the afternoon of every day after culturing for 20-40 days, changing the water once at every three days, and the like; 2, feed management: (1), ensuring the fact that the feeding frequency is different according to different culture time; (2), adding shrimp and crab nutrients, immune polysaccharides and rice vinegar to the fed feed after culturing for 30 days; (3), controlling the feeding amount after the total feeding amount per mu at every day is stable; 3, emergency processing and the like. According to the disease comprehensive prevention and control method for the greenhouse-cultured penaeus vannamei, the explosion of shrimp diseases can be prevented, and the survival rate and the growth rate of penaeus in the culture procedure can also be remarkably increased.