The aim of this study was to evaluate the in vitro and in vivo susceptibility of Trypanosoma evansi to α-Bisabolol and solid lipid nanoparticles containing α-Bisabolol (SLN-B). In vitro, a trypanocidal effect of α-Bisabolol and SLN-B was observed when used at 0.5, 1 and 2% concentrations, i.e., the concentrations of 1 and 2% showed a faster trypanocidal effect when compared to chemotherapy (diminazene aceturate - D.A.). T. evansi infected mice were treated with α-Bisabolol and SLN-B at a dose of 1.0 mL kg-1 during seven days via oral gavage. In vivo, treatment with SLN-B, D.A. and D.A. associated with SLN-B were able to increase (p < 0.05) the pre-patent period and longevity when compared to positive control (infected and untreated animals), but showed no curative efficacy. T. evansi infected mice treated with D.A. associate with SLN-B, where a curative efficacy of 50% was found, a much better result when D. A and SLN-B were used alone (16.66%). In summary, the association with D. A + SLN-B can be used as an alternative to improve the therapeutic effectiveness of D.A., and for treatment of infected animals with T. evansi. Also, the nanotechnology associated with natural products arises an important alternative for the improve the trypanocidal action.