Aims This study investigated the adaptation strategies of Pseudomonas protegens to hyperosmotic growth environments (HGE). Methods and Results The current study combined transcriptomics and proteomics to provide an overview of the molecular mechanism of P. protegens adaptation to HGE. The results revealed that HGE exerted prominent impact on the synthesis of proteins involved in multiple cellular functions. Comparison of the differentially accumulated proteins at both transcriptomics and proteomics levels indicated the existence of complex post-transcriptional modification during P. protegens hyperosmotic adaptation. Conclusions During HGE adaptation, the cells form a complex self-protection mechanism. Significance and Impact of the Study The results of the current study can help researchers to gain insights regarding the mechanism of P. protegens adaptation to HGE. These findings provide information for the application of stress methods and facilitate its broad commercial utilization.