The effectiveness of some plant extracts to protect against pests enhancing the natural defensive responses of the plant has been reported. Plant extract of Mimosa tenuifloraand Quercus robur has promising potential to reduce the incidence of a wide range of phytopathogenic fungi due to its antimicrobial compounds. In this study, we aimed to elucidate the effectiveness and mode of action of this mix extract in Lactuca sativa against Sclerotinia sclerotiorum. To achieve this objective, 4 weeks old lettuce plants of cv.Romana were treated with 2 cc l -1 of the plant extract either by soil drench or foliar applications 72 hours before the inoculation. The treatments were able to significantly reduce the progression of the pathogen, decreasing the diameter of the infection by 32% and 17% in foliar and soil drench application, respectively. Moreover, the results showed significantly higher levels of hydrogen peroxide (H2O2) as well as callose deposition in plants treated and inoculated compared with non-treated plants. However, no direct effect on the fungus growth was observed in vitro suggesting that foliar and root treatments with M. tenuiflora and Q. robur extract significantly reduce the infection of S. sclerotiorum in leaves of lettuce, through the strengthening of the wall mediated by the deposition of callose and the release of H2O2. The fact that the treatment enhances different processes involved in plant innate defense indicates that this treatment is acting as a resistant inducer, and could be effective against different microorganisms.