As part of our continuous research for the discovery of bioactive compounds against Trypanosoma cruzi and Leishmania infantum, the alkaloid (6aS)-dicentrine (1) was oxidized to afford (6aS,6S)- (2) and (6aS,6R)- (3) dicentrine-N-oxides. Evaluation of the cytotoxicity against NCTC cells indicated that 2 and 3 are non-toxic (CC₅₀>200 μM) whereas 1 demonstrated CC₅₀ of 52.0 μM. Concerning T. cruzi activity against amastigotes, derivatives 2 and 3 exhibited EC₅₀ values of 9.9 μM (SI>20.2) and 27.5 μM (SI>7.3), respectively, but 1 is inactive (EC₅₀>100 μM). Otherwise, when tested against L. infantum amastigotes, 1 and 3 exhibited EC₅₀ values of 10.3 μM (SI=5.0) and 12.7 μM (SI>15.7), respectively, being 2 inactive (EC₅₀>100 μM). Comparing the effects of positive controls benznidazol (EC₅₀=6.5 μM and SI>30.7) and miltefosine (EC₅₀=10.2 μM and SI=15.2), it was observed a selective antiparasitic activity to diastereomers 2 and 3 against T. cruzi and L. infantum. Considering stereochemical aspects, it was suggested that the configuration of the new stereocenter formed after oxidation of 1 played an important role in the bioactivity against amastigotes of both tested parasites.