Irrigated agriculture is responsible for a third of global agricultural production, but the overuse of water resources and intensification of farming practices threaten its sustainability. The use of saline water in irrigation has become an alternative in areas subjected to frequent drought, but this practice affects plant growth due to osmotic impact and excess of ions. Plant-growth-promoting rhizobacteria (PGPR) can mitigate the negative impacts of salinity and other abiotic factors on crop yields.Actinobacteriafrom the hyper-arid Atacama Desert could increase the plant tolerance to salinity, allowing their use as biofertilizers for lettuce crops using waters with high salt contents. In this work, rhizosphere samples of halophyticMetharme lanatawere obtained from Atacama Desert, and actinobacteria were isolated and identified by 16S gene sequencing. The PGPR activities of phosphate solubilization, nitrogen fixation, and the production of siderophore and auxin were assessed at increasing concentrations of NaCl, as well as the enhancement of salt tolerance in lettuce plants irrigated with 100 mM of NaCl. Photosynthesis activity and chlorophyll content, proline content, lipid peroxidation, cation and P concentration, and the identification and quantification of phenolic compounds were assessed. The strainsS. niveoruberATMLC132021 andS. lienomyciniATMLC122021 were positive for nitrogen fixation and P solubilization activities and produced auxin up to 200 mM NaCl. In lettuce plants, both strains were able to improve salt stress tolerance by increasing proline contents, carotenoids, chlorophyll, water use efficiency (WUE), stomatal conductance (gs), and net photosynthesis (A), concomitantly with the overproduction of the phenolic compound dicaffeoylquinic acid. All these traits were positively correlated with the biomass production under saltwater irrigation, suggesting its possible use as bioinoculants for the agriculture in areas where the water resources are scarce and usually with high salt concentrations.