A large number of studies have demonstrated the implication of oxidative stress (OxS) in the pathogenesis of ageing-related muscle decline and atrophy. The key mechanism is related to the OxS-induced production of free radicals, with the consequent increase in oxidative damage, resulting in affected muscle quality and strength. The present study aimed to evaluate the efficacy of a grape polyphenol-based nutraceutical formulation (Taurisolo®) in reducing the OxS in muscle of aged rats. A group of 16 aged (20 months) rats were orally administered with Taurisolo® (n = 8; 100 mg/kg Taurisolo®) or placebo (n = 8; 50 mg/kg maltodextrin); an additional group of eight young (three months) rats were also treated with placebo. All the treatments were orally administered for 30 days. The activities of antioxidant enzymes, the levels of malondialdehyde (MDA) and nitrotyrosine (N-Tyr) and the expression of OxS- and inflammation-related genes were evaluated on the gastrocnemius muscle. In muscle samples of the treated-group, increased activity of antioxidant enzymes, reduced MDA and N-Tyr levels and increased expression of antioxidant and anti-inflammatory genes were observed in respect to the placebo. Data herein presented suggest that the chronic treatment with Taurisolo® significantly reduces oxidative damage and improves muscle performance in aged rats.