COMP-4, a nutraceutical combination consisting of ginger rhizome, muira puama, Paullinia cupana, and L-citrulline, enhances intracellular nitric oxide (NO) production by the corporal smooth muscle cells (CSMC). This study aims to determine if the previously shown beneficial effect of COMP-4 on the histology and function of the aging penis is associated with an antioxidative effect from endogenously produced NO. Ten-month-old male rats were treated daily for 2 months with COMP-4 or vehicle at which time the corpora and penile dorsal artery (PDA) were evaluated by immunohistochemistry for (a) apoptosis (b) proliferative cell nuclear antigen, (c) heme oxygenase-1 (HO-1), (d) myeloperoxidase (MPO), and (e) nitrotyrosine (NT). CSMC were cultured and incubated with COMP-4 in order to determine intracellular oxidative stress via the GSH/GSSG ratio. In both the corpora and PDA, daily treatment with COMP-4 resulted in an increase in both smooth muscle cell proliferation and HO-1 expression as well as a decrease in MPO. There was no change in either apoptosis or NT expression. In the CSMC cell culture, treatment with COMP-4 increased the intracellular GSH/GSSG ratio. COMP-4 appears to have an antioxidant effect on the aging vascular smooth muscle cells both in the corpora and peripheral vasculature.