This study explored the effect of pterostilbene (PTS) complexed with hydroxypropyl-β-cyclodextrin (HPβCD) on right heart function, glutathione and glutaredoxin systems and the expression of intracellular calcium handling redox-sensitive proteins in the experimental model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). After 7 days of PAH induction, rats received daily doses of the PTS:HPβCD complex (corresponding to 25, 50 or 100 mg kg-1 of PTS) or vehicle (control group, CTR0) (an aqueous solution containing HPβCD, CTR0 and MCT0) via oral administration during two weeks. The results showed that the PTS:HPβCD complex increased the content of reduced glutathione and the activity of glutathione-S-transferase and glutaredoxin in the right ventricle (RV) of MCT-treated rats in a dose-dependent manner. Additionally, at higher doses, it also prevented the reduction of stroke volume and cardiac output, prevented MPI increase, reduced lipoperoxidation, reduced total phospholamban, and increased the expression of SERCA in the RV of MCT-treated rats. These results demonstrate that the PTS:HPβCD complex has a dose-dependent antioxidant mechanism that results in improved cardiac function in experimental right heart failure. Our results open a field of possibilities to PTS administration as new therapeutic approach to conventional therapy for right ventricular dysfunction. Novelty bullets: – Pterostilbene complexed with hydroxypropyl-β-cyclodextrin could be a new therapeutic approach; – Pterostilbene complexed with hydroxypropyl-β-cyclodextrin re-establishes redox homeostasis, through glutathione metabolism modulation, leading to an improved myocardial performance index in pulmonary arterial hypertension-provoked right heart failure.