The tolerance of plant growth-promoting endophytes (PGPEs) against various concentrations of cadmium (Cd) and nickel (Ni) was investigated. Two glutathione-producing bacterial strains ( Enterobacter ludwigii SAK5 and Exiguobacterium indicum SA22) were screened for Cd and Ni accumulation and tolerance in contaminated media, which showed resistance up to 1.0 mM. Both strains were further evaluated by inoculating specific plants with the bacteria for five days prior to heavy metal treatment (0.5 and 1.0 mM). The enhancement of biomass and growth attributes such as the root length, shoot length, root fresh weight, shoot fresh weight, and chlorophyll content were compared between treated inoculated plants and treated non-inoculated plants. Both strains significantly increased the accumulation of Cd and Ni in inoculated plants. The accumulation of both heavy metals was higher in the roots than in the shoots, however; Ni accumulation was greater than Cd. Heavy metal stress-responsive genes such as OsGST, OsMTP1, and OsPCS1 were significantly upregulated in treated non-inoculated plants compared with treated inoculated plants, suggesting that both strains reduced heavy metal stress. Similarly, abscisic acid (ABA) was increased with increased heavy metal concentration; however, it was reduced in inoculated plants compared with non-inoculated plants. Salicylic acid (SA) was found to exert synergistic effects with ABA. The application of suitable endophytic bacteria can protect against heavy metal hyperaccumulation by enhancing detoxification mechanisms.