High concentration of heavy metal (HM) is toxic to the plant and endophytes can improve host plants HM tolerance. In the present study, the role of endophytes FT2G7 (Phomopsis columnaris) and FT2G24 (Setophoma terrestris) on host plant Dysphania ambrosioides HM tolerance was evaluated under multi-HMs stress through pot experiments. The results showed that regardless at lower or higher multi-HMs stress, inoculation of isolate(s) improved host plants growth and HM tolerance through regulating their antioxidant capacities etc., and inoculation of multi-isolates (ME+) had better effects on host plants than inoculation of single isolate (SE+). Particularly, the malondialdehyde (MDA) of ME+ decreased 50% under the lower multi-HMs stress and the glutathione (GSH) increased 169.55% under the higher multi-HMs stress when compared with ME-. Both inoculation of single isolate and multi-isolates increased host plants HM accumulation when compared with non-inoculation. However, different isolates had different effects: under the lower multi-HMs stress, the accumulation of multi-HMs in ME+ plants was higher than that of V12G7-inoculated plants but lower than that of FT2G24-inoculated plants, with a few exceptions, such as Zn in underground parts of ME+ was higher than that of FT2G24-inoculated plants. The bioaccumulation factor (BAF) of ME+ was higher than that of SE+, but the translocation factor (TF) was lower than that of SE+, except Pb of FT2G24 inoculated plants. Under the higher multi-HMs stress, Zn and Cd in ME+ plants were lower but Pb was higher than that of SE+, with a few exceptions, such as Pb in underground parts of ME+ plants was lower than that of FT2G24-inoculated plants. The BAF and TF of ME+ were lower than that of SE+, except that of Pb.