Jumbo squid (Dosidicus gigas) is one of the most important squid species worldwide. However, it is highly perishable due to microbial spoilage. Here, we demonstrated a soaking treatment using ozone-microbubble (OMB) water as an alternative disinfection platform for squid decontamination prior to refrigerated storage. Compared with the control treatment (soaking squids with reverse osmosis water for 5 min [RO5]), soaking squids with OMB for 3 min (OMB3) was revealed to optimally reducing the growth of microbiological contaminants (e.g., TPC and coliform) and maintaining the squid qualities (e.g., TVBN, ammonia, and color). Unlike RO5-treated squids, the microstructure of OMB3-treated squids was intact and uniform in size, which is similar to the general structure of the raw ones'. OMB3 also retarded the pink discoloration caused by pigments released from squid chromatophores. Moreover, OMB3 was able to delay the chromatophore damage in squid skin, consequently retarding pigment release and color change throughout storage periods. Overall, this study demonstrated the effectiveness of OMB as a potential disinfection agent and preventative measure for squids without severely affecting their qualities.