Recent studies suggest that subjects with hypothyroidism under therapy with levothyroxine (L-T4) might develop oxidative stress. The aim of this study was to test a redox-balance modulator, fermented papaya-based nutraceutical (FPP), together with subclinical (SH) or mild hypothyroidism (MH) treatment in view of biochemical changes. A total of 60 females treated for SH-MH were divided into two matched groups and received either FPP 3 grams 1 sachet three times a day (t.i.d.) or placebo for 3 months. A significant baseline increase of all oxidative markers was observed in SH-MH (p<0.05 vs. control) and even more under T4 treatment (p<0.05). FPP caused a normalization of redox markers (p<0.01 vs. placebo). Thyroid supplementation accelerates mitochondrial oxygen consumption and oxidative stress, whereas a redox-modulator therapy is advisable, given the long-lasting treatment in such cases.